Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 271369

Special Issue Editors

Department of Science and Engineering of Oxide Materials and Nanomaterials, University Politehnica of Bucharest, 011061 Bucharest, Romania
Interests: nanomaterials; drug delivery systems; biomimetic materials; biogenic calcium sources; composite scaffolds
Special Issues, Collections and Topics in MDPI journals
Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 060042 Bucharest, Romania
Interests: inorganic materials; re-generating (raw) materials; end-of-life products; innovative bionanomaterials; transmission electron microscopy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The aim of this Special Issue is to gather latest studies which creatively combine classic concepts of materials processing with those of waste management, leading to sustainable tissue engineering. The majority of current technologies for drug delivery systems and tissue regeneration involves synthetic materials, with no biological activity, which already proved to be “biologically safe” but, unfortunately, are highly unlikely to succeed in the long term. Prospective alternatives should be based on active, biomimetic templates which can biologically and mechanically participate in the stimulation of tissue regeneration. Sustainable materials for drug delivery and tissue regeneration can be easily obtained by the conversion of biogenic waste with chemical value into valuable materials. Their low cost, high availability, and non-toxic nature recommend them for this kind of application, reducing at the same time the pollution generated by the accumulation of such industrial byproducts.

The results of this Special Issue are expected to be of significant benefit for industry, the environment, and society. The industry will progress in developing an ecological, simple and cheap way to implement technology, in favor of a healthier community. 

Dr. Ionela Andreea Neacsu
Dr. Bogdan Stefan Vasile
Guest Editors

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Keywords

  • drug delivery
  • cutaneous delivery
  • oral delivery
  • controlled drug release
  • sustainable tissue engineering
  • 3D bioprinting
  • sustainable materials
  • transdermal patches
  • natural compounds
  • Bio-template
  • biogenic waste recovery
  • green materials
  • eco-friendly
  • cell proliferation

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Published Papers (103 papers)

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17 pages, 2432 KiB  
Article
Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous
by Seher Yaylaci, Erdem Dinç, Bahri Aydın, Ayse B. Tekinay and Mustafa O. Guler
Pharmaceutics 2023, 15(4), 1264; https://doi.org/10.3390/pharmaceutics15041264 - 18 Apr 2023
Cited by 5 | Viewed by 1277
Abstract
Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative [...] Read more.
Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature—a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye’s posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration. Full article
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20 pages, 20390 KiB  
Article
A New Strategy for Nucleic Acid Delivery and Protein Expression Using Biocompatible Nanohydrogels of Predefined Sizes
by Lakshmanan Eswaran, Gila Kazimirsky, Ronen Yehuda and Gerardo Byk
Pharmaceutics 2023, 15(3), 961; https://doi.org/10.3390/pharmaceutics15030961 - 16 Mar 2023
Cited by 1 | Viewed by 1160
Abstract
We have developed new formulations of nanohydrogels (NHGs) complexed with DNA devoid of cell toxicity, which, together with their tuned sizes, makes them of great interest for delivering DNA/RNA for foreign protein expression. Transfection results demonstrate that, unlike classical lipo/polyplexes, the new NHGs [...] Read more.
We have developed new formulations of nanohydrogels (NHGs) complexed with DNA devoid of cell toxicity, which, together with their tuned sizes, makes them of great interest for delivering DNA/RNA for foreign protein expression. Transfection results demonstrate that, unlike classical lipo/polyplexes, the new NHGs can be incubated indefinitely with cells without apparent cellular toxicity, resulting in the high expression of foreign proteins for long periods of time. Although protein expression starts with a delay as compared to classical systems, it is sustained for a long period of time, even after passing cells without observation of toxicity. A fluorescently labelled NHG used for gene delivery was detected inside cells very early after incubation, but the protein expression was delayed by many days, demonstrating that there is a time-dependent release of genes from the NHGs. We suggest that this delay is due to the slow but continuous release of DNA from the particles concomitantly with slow but continuous protein expression. Additionally, results obtained after the in vivo administration of m-Cherry/NHG complexes indicated a delayed but prolonged expression of the marker gene in the tissue of administration. Overall, we have demonstrated gene delivery and foreign protein expression using GFP and m-Cherry marker genes complexed with biocompatible nanohydrogels. Full article
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20 pages, 4527 KiB  
Article
Dexamethasone and Dexamethasone Phosphate: Effect on DMPC Membrane Models
by Candelaria Ines Cámara, Matías Ariel Crosio, Ana Valeria Juarez and Natalia Wilke
Pharmaceutics 2023, 15(3), 844; https://doi.org/10.3390/pharmaceutics15030844 - 04 Mar 2023
Cited by 2 | Viewed by 1352
Abstract
Dexamethasone (Dex) and Dexamethasone phosphate (Dex-P) are synthetic glucocorticoids with high anti-inflammatory and immunosuppressive actions that gained visibility because they reduce the mortality in critical patients with COVID-19 connected to assisted breathing. They have been widely used for the treatment of several diseases [...] Read more.
Dexamethasone (Dex) and Dexamethasone phosphate (Dex-P) are synthetic glucocorticoids with high anti-inflammatory and immunosuppressive actions that gained visibility because they reduce the mortality in critical patients with COVID-19 connected to assisted breathing. They have been widely used for the treatment of several diseases and in patients under chronic treatments, thus, it is important to understand their interaction with membranes, the first barrier when these drugs get into the body. Here, the effect of Dex and Dex-P on dimyiristoylphophatidylcholine (DMPC) membranes were studied using Langmuir films and vesicles. Our results indicate that the presence of Dex in DMPC monolayers makes them more compressible and less reflective, induces the appearance of aggregates, and suppresses the Liquid Expanded/Liquid Condensed (LE/LC) phase transition. The phosphorylated drug, Dex-P, also induces the formation of aggregates in DMPC/Dex-P films, but without disturbing the LE/LC phase transition and reflectivity. Insertion experiments demonstrate that Dex induces larger changes in surface pressure than Dex-P, due to its higher hydrophobic character. Both drugs can penetrate membranes at high lipid packings. Vesicle shape fluctuation analysis shows that Dex-P adsorption on GUVs of DMPC decreases membrane deformability. In conclusion, both drugs can penetrate and alter the mechanical properties of DMPC membranes. Full article
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17 pages, 7721 KiB  
Article
Hydrophilic High Drug-Loaded 3D Printed Gastroretentive System with Robust Release Kinetics
by Gloria Mora-Castaño, Mónica Millán-Jiménez and Isidoro Caraballo
Pharmaceutics 2023, 15(3), 842; https://doi.org/10.3390/pharmaceutics15030842 - 04 Mar 2023
Cited by 4 | Viewed by 1463
Abstract
Three-dimensional printing (3DP) technology enables an important improvement in the design of new drug delivery systems, such as gastroretentive floating tablets. These systems show a better temporal and spatial control of the drug release and can be customized based on individual therapeutic needs. [...] Read more.
Three-dimensional printing (3DP) technology enables an important improvement in the design of new drug delivery systems, such as gastroretentive floating tablets. These systems show a better temporal and spatial control of the drug release and can be customized based on individual therapeutic needs. The aim of this work was to prepare 3DP gastroretentive floating tablets designed to provide a controlled release of the API. Metformin was used as a non-molten model drug and hydroxypropylmethyl cellulose with null or negligible toxicity was the main carrier. High drug loads were assayed. Another objective was to maintain the release kinetics as robust as possible when varying drug doses from one patient to another. Floating tablets using 10–50% w/w drug-loaded filaments were obtained by Fused Deposition Modelling (FDM) 3DP. The sealing layers of our design allowed successful buoyancy of the systems and sustained drug release for more than 8 h. Moreover, the effect of different variables on the drug release behaviour was studied. It should be highlighted that the robustness of the release kinetics was affected by varying the internal mesh size, and therefore the drug load. This could represent a step forward in the personalization of the treatments, a key advantage of 3DP technology in the pharmaceutical field. Full article
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33 pages, 14960 KiB  
Article
Composite PLGA–Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration
by Georgia K. Pouroutzidou, Lambrini Papadopoulou, Maria Lazaridou, Konstantinos Tsachouridis, Chrysanthi Papoulia, Dimitra Patsiaoura, Ioannis Tsamesidis, Konstantinos Chrissafis, George Vourlias, Konstantinos M. Paraskevopoulos, Antonios D. Anastasiou, Dimitrios N. Bikiaris and Eleana Kontonasaki
Pharmaceutics 2023, 15(3), 819; https://doi.org/10.3390/pharmaceutics15030819 - 02 Mar 2023
Cited by 5 | Viewed by 1745
Abstract
Silica-based ceramics doped with calcium and magnesium have been proposed as suitable materials for scaffold fabrication. Akermanite (Ca2MgSi2O7) has attracted interest for bone regeneration due to its controllable biodegradation rate, improved mechanical properties, and high apatite-forming ability. [...] Read more.
Silica-based ceramics doped with calcium and magnesium have been proposed as suitable materials for scaffold fabrication. Akermanite (Ca2MgSi2O7) has attracted interest for bone regeneration due to its controllable biodegradation rate, improved mechanical properties, and high apatite-forming ability. Despite the profound advantages, ceramic scaffolds provide weak fracture resistance. The use of synthetic biopolymers such as poly(lactic-co-glycolic acid) (PLGA) as coating materials improves the mechanical performance of ceramic scaffolds and tailors their degradation rate. Moxifloxacin (MOX) is an antibiotic with antimicrobial activity against numerous aerobic and anaerobic bacteria. In this study, silica-based nanoparticles (NPs) enriched with calcium and magnesium, as well as copper and strontium ions that induce angiogenesis and osteogenesis, respectively, were incorporated into the PLGA coating. The aim was to produce composite akermanite/PLGA/NPs/MOX-loaded scaffolds through the foam replica technique combined with the sol–gel method to improve the overall effectiveness towards bone regeneration. The structural and physicochemical characterizations were evaluated. Their mechanical properties, apatite forming ability, degradation, pharmacokinetics, and hemocompatibility were also investigated. The addition of NPs improved the compressive strength, hemocompatibility, and in vitro degradation of the composite scaffolds, resulting in them keeping a 3D porous structure and a more prolonged release profile of MOX that makes them promising for bone regeneration applications. Full article
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19 pages, 22734 KiB  
Article
3D-Printing of Silk Nanofibrils Reinforced Alginate for Soft Tissue Engineering
by Zahra Mohammadpour, Mahshid Kharaziha and Ali Zarrabi
Pharmaceutics 2023, 15(3), 763; https://doi.org/10.3390/pharmaceutics15030763 - 24 Feb 2023
Cited by 12 | Viewed by 1649
Abstract
The main challenge of extrusion 3D bioprinting is the development of bioinks with the desired rheological and mechanical performance and biocompatibility to create complex and patient-specific scaffolds in a repeatable and accurate manner. This study aims to introduce non-synthetic bioinks based on alginate [...] Read more.
The main challenge of extrusion 3D bioprinting is the development of bioinks with the desired rheological and mechanical performance and biocompatibility to create complex and patient-specific scaffolds in a repeatable and accurate manner. This study aims to introduce non-synthetic bioinks based on alginate (Alg) incorporated with various concentrations of silk nanofibrils (SNF, 1, 2, and 3 wt.%) and optimize their properties for soft tissue engineering. Alg-SNF inks demonstrated a high degree of shear-thinning with reversible stress softening behavior contributing to extrusion in pre-designed shapes. In addition, our results confirmed the good interaction between SNFs and alginate matrix resulted in significantly improved mechanical and biological characteristics and controlled degradation rate. Noticeably, the addition of 2 wt.% SNF improved the compressive strength (2.2 times), tensile strength (5 times), and elastic modulus (3 times) of alginate. In addition, reinforcing 3D-printed alginate with 2 wt.% SNF resulted in increased cell viability (1.5 times) and proliferation (5.6 times) after 5 days of culturing. In summary, our study highlights the favorable rheological and mechanical performances, degradation rate, swelling, and biocompatibility of Alg-2SNF ink containing 2 wt.% SNF for extrusion-based bioprinting. Full article
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26 pages, 4560 KiB  
Article
HER2-Specific Peptide (LTVSPWY) and Antibody (Herceptin) Targeted Core Cross-Linked Micelles for Breast Cancer: A Comparative Study
by Nazende Nur Bayram, Gizem Tuğçe Ulu, Nusaibah Abdulsalam Abdulhadi, Seda Gürdap, İsmail Alper İşoğlu, Yusuf Baran and Sevil Dinçer İşoğlu
Pharmaceutics 2023, 15(3), 733; https://doi.org/10.3390/pharmaceutics15030733 - 22 Feb 2023
Viewed by 2107
Abstract
This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfobetaine ((N-3-sulfopropyl-N,N-dimethylamonium)ethyl [...] Read more.
This study aims to prepare a novel breast cancer-targeted micelle-based nanocarrier, which is stable in circulation, allowing intracellular drug release, and to investigate its cytotoxicity, apoptosis, and cytostatic effects, in vitro. The shell part of the micelle is composed of zwitterionic sulfobetaine ((N-3-sulfopropyl-N,N-dimethylamonium)ethyl methacrylate), while the core part is formed by another block, consisting of AEMA (2-aminoethyl methacrylamide), DEGMA (di(ethylene glycol) methyl ether methacrylate), and a vinyl-functionalized, acid-sensitive cross-linker. Following this, a targeting agent (peptide (LTVSPWY) and antibody (Herceptin®)), in varying amounts, were coupled to the micelles, and they were characterized by 1H NMR, FTIR (Fourier-transform infrared spectroscopy), Zetasizer, BCA protein assay, and fluorescence spectrophotometer. The cytotoxic, cytostatic, apoptotic, and genotoxic effects of doxorubicin-loaded micelles were investigated on SKBR-3 (human epidermal growth factor receptor 2 (HER2)-positive) and MCF10-A (HER2-negative). According to the results, peptide-carrying micelles showed a higher targeting efficiency and better cytostatic, apoptotic, and genotoxic activities than antibody-carrying and non-targeted micelles. Also, micelles masked the toxicity of naked DOX on healthy cells. In conclusion, this nanocarrier system has great potential to be used in different drug-targeting strategies, by changing targeting agents and drugs. Full article
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19 pages, 4929 KiB  
Article
Synthesis of Magnetic Iron Oxide-Incorporated Cellulose Composite Particles: An Investigation on Antioxidant Properties and Drug Delivery Applications
by Arifa Naznin, Palash Kumar Dhar, Sagar Kumar Dutta, Sumon Chakrabarty, Utpal Kumar Karmakar, Pritam Kundu, Muhammad Sarwar Hossain, Hasi Rani Barai and Md. Rezaul Haque
Pharmaceutics 2023, 15(3), 732; https://doi.org/10.3390/pharmaceutics15030732 - 22 Feb 2023
Cited by 5 | Viewed by 1768
Abstract
In recent years, polymer-supported magnetic iron oxide nanoparticles (MIO-NPs) have gained a lot of attention in biomedical and healthcare applications due to their unique magnetic properties, low toxicity, cost-effectiveness, biocompatibility, and biodegradability. In this study, waste tissue papers (WTP) and sugarcane bagasse (SCB) [...] Read more.
In recent years, polymer-supported magnetic iron oxide nanoparticles (MIO-NPs) have gained a lot of attention in biomedical and healthcare applications due to their unique magnetic properties, low toxicity, cost-effectiveness, biocompatibility, and biodegradability. In this study, waste tissue papers (WTP) and sugarcane bagasse (SCB) were utilized to prepare magnetic iron oxide (MIO)-incorporated WTP/MIO and SCB/MIO nanocomposite particles (NCPs) based on in situ co-precipitation methods, and they were characterized using advanced spectroscopic techniques. In addition, their anti-oxidant and drug-delivery properties were investigated. Field emission scanning electron microscopy (FESEM) and X-ray diffraction (XRD) analyses revealed that the shapes of the MIO-NPs, SCB/MIO-NCPs, and WTP/MIO-NCPs were agglomerated and irregularly spherical with a crystallite size of 12.38 nm, 10.85 nm, and 11.47 nm, respectively. Vibrational sample magnetometry (VSM) analysis showed that both the NPs and the NCPs were paramagnetic. The free radical scavenging assay ascertained that the WTP/MIO-NCPs, SCB/MIO-NCPs, and MIO-NPs exhibited almost negligible antioxidant activity in comparison to ascorbic acid. The swelling capacities of the SCB/MIO-NCPs and WTP/MIO-NCPs were 155.0% and 159.5%, respectively, which were much higher than the swelling efficiencies of cellulose-SCB (58.3%) and cellulose-WTP (61.6%). The order of metronidazole drug loading after 3 days was: cellulose-SCB < cellulose-WTP < MIO-NPs < SCB/MIO-NCPs < WTP/MIO-NCPs, whereas the sequence of the drug-releasing rate after 240 min was: WTP/MIO-NCPs < SCB/MIO-NCPs < MIO-NPs < cellulose-WTP < cellulose-SCB. Overall, the results of this study showed that the incorporation of MIO-NPs in the cellulose matrix increased the swelling capacity, drug-loading capacity, and drug-releasing time. Therefore, cellulose/MIO-NCPs obtained from waste materials such as SCB and WTP can be used as a potential vehicle for medical applications, especially in a metronidazole drug delivery system. Full article
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13 pages, 5920 KiB  
Article
Intracellular Delivery of Itaconate by Metal–Organic Framework-Anchored Hydrogel Microspheres for Osteoarthritis Therapy
by Han Yu, Peng Ren, Xuekang Pan, Xinyu Zhang, Jun Ma, Jiayi Chen, Jian Sheng, Huanhuan Luo, Huigen Lu and Gang Chen
Pharmaceutics 2023, 15(3), 724; https://doi.org/10.3390/pharmaceutics15030724 - 22 Feb 2023
Cited by 5 | Viewed by 1666
Abstract
Treatment of osteoarthritis (OA) remains a significant clinical challenge. Itaconate (IA), an emerging regulator of intracellular inflammation and oxidative stress, may potentially be harnessed to treat OA. However, the short joint residence time, inefficient drug delivery, and cell-impermeable property of IA can seriously [...] Read more.
Treatment of osteoarthritis (OA) remains a significant clinical challenge. Itaconate (IA), an emerging regulator of intracellular inflammation and oxidative stress, may potentially be harnessed to treat OA. However, the short joint residence time, inefficient drug delivery, and cell-impermeable property of IA can seriously hamper the clinical translation. Herein, IA-encapsulated zeolitic imidazolate framework-8 (IA-ZIF-8) nanoparticles were self-assembled by zinc ions, 2-methylimidazole, and IA to render them pH-responsive. Subsequently, IA-ZIF-8 nanoparticles were firmly immobilized in hydrogel microspheres via one-step microfluidic technology. It was demonstrated in vitro experiments that IA-ZIF-8-loaded hydrogel microspheres (IA-ZIF-8@HMs) exhibited good anti-inflammatory and anti-oxidative stress effects by releasing pH-responsive nanoparticles into chondrocytes. Importantly, compared with IA-ZIF-8, IA-ZIF-8@HMs showed better performance in the treatment of OA due to their superior performance in sustained release. Thus, such hydrogel microspheres not only hold enormous potential for OA therapy, but also provide a novel avenue for cell-impermeable drugs by constructing appropriate drug delivery systems. Full article
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17 pages, 4756 KiB  
Article
The Ability of Some Polysaccharides to Disaggregate Lysozyme Amyloid Fibrils and Renature the Protein
by Olga Makshakova, Liliya Bogdanova, Dzhigangir Faizullin, Diliara Khaibrakhmanova, Sufia Ziganshina, Elena Ermakova, Yuriy Zuev and Igor Sedov
Pharmaceutics 2023, 15(2), 624; https://doi.org/10.3390/pharmaceutics15020624 - 13 Feb 2023
Cited by 4 | Viewed by 1532
Abstract
The deposition of proteins in the form of insoluble amyloid fibril aggregates is linked to a range of diseases. The supramolecular architecture of such deposits is governed by the propagation of β-strands in the direction of protofilament growth. In the present study, we [...] Read more.
The deposition of proteins in the form of insoluble amyloid fibril aggregates is linked to a range of diseases. The supramolecular architecture of such deposits is governed by the propagation of β-strands in the direction of protofilament growth. In the present study, we analyze the structural changes of hen egg-white lysozyme fibrils upon their interactions with a range of polysaccharides, using AFM and FTIR spectroscopy. Linear anionic polysaccharides, such as κ-carrageenan and sodium alginate, are shown to be capable to disaggregate protofilaments with eventual protein renaturation. The results help to understand the mechanism of amyloid disaggregation and create a platform for both the development of new therapeutic agents for amyloidose treatment, and the design of novel functional protein–polysaccharide complex-based nanomaterials. Full article
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29 pages, 6973 KiB  
Article
Intranasal Delivery of a Silymarin Loaded Microemulsion for the Effective Treatment of Parkinson’s Disease in Rats: Formulation, Optimization, Characterization, and In Vivo Evaluation
by Mohd Imran, Mazen Almehmadi, Ahad Amer Alsaiari, Mehnaz Kamal, Mohammed Kanan Alshammari, Mohammed Omar Alzahrani, Faisal Khaled Almaysari, Abdulrahman Omar Alzahrani, Ahmed Faraj Elkerdasy and Sachin Kumar Singh
Pharmaceutics 2023, 15(2), 618; https://doi.org/10.3390/pharmaceutics15020618 - 12 Feb 2023
Cited by 5 | Viewed by 2079
Abstract
A mucoadhesive microemulsion of lipophilic silymarin (SLMMME) was developed to treat Parkinson’s disease (PD). Optimization of the SLM microemulsion (ME) was performed using Central Composite Design (CCD). The composition of oil, surfactant, co-surfactant, and water was varied, as per the design, to optimize [...] Read more.
A mucoadhesive microemulsion of lipophilic silymarin (SLMMME) was developed to treat Parkinson’s disease (PD). Optimization of the SLM microemulsion (ME) was performed using Central Composite Design (CCD). The composition of oil, surfactant, co-surfactant, and water was varied, as per the design, to optimize their ratio and achieve desirable droplet size, zeta potential, and drug loading. The droplet size, zeta potential, and drug loading of optimized SLMME were 61.26 ± 3.65 nm, −24.26 ± 0.2 mV, and 97.28 ± 4.87%, respectively. With the addition of chitosan, the droplet size and zeta potential of the developed ME were both improved considerably. In vitro cell toxicity investigations on a neuroblastoma cell line confirmed that SLMMME was non-toxic and harmless. In comparison to ME and drug solution, mucoadhesive ME had the most flow through sheep nasal mucosa. Further, the in vitro release showed significantly higher drug release, and diffusion of the SLM loaded in MEs than that of the silymarin solution (SLMS). The assessment of behavioral and biochemical parameters, as well as inflammatory markers, showed significant (p < 0.05) amelioration in their level, confirming the significant improvement in neuroprotection in rats treated with SLMMME compared to rats treated with naïve SLM. Full article
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13 pages, 1634 KiB  
Article
Development of Autopolymerizing Resin Material with Antimicrobial Properties Using Montmorillonite and Nanoporous Silica
by Shuhei Otsubo, Ko Nakanishi, Kakufu Fukukawa, Ryoshun Endo, Seiichiro Yoshida, Aiko Matsumoto, Kumiko Yoshihara, Tsukasa Akasaka, Akira Hasebe, Yasuhiro Yoshida and Yoshiaki Sato
Pharmaceutics 2023, 15(2), 544; https://doi.org/10.3390/pharmaceutics15020544 - 06 Feb 2023
Viewed by 1297
Abstract
Although autopolymerizing resin offers numerous applications in orthodontic treatment, plaque tends to accumulate between the appliance and the mucosa, which increases the number of microorganisms present. In this study, we added cetylpyridinium chloride (CPC) loaded montmorillonite (Mont) and nanoporous silica (NPS) to autopolymerizing [...] Read more.
Although autopolymerizing resin offers numerous applications in orthodontic treatment, plaque tends to accumulate between the appliance and the mucosa, which increases the number of microorganisms present. In this study, we added cetylpyridinium chloride (CPC) loaded montmorillonite (Mont) and nanoporous silica (NPS) to autopolymerizing resin (resin-Mont, resin-NPS) and evaluated their drug release capacity, antimicrobial capacity, drug reuptake capacity, mechanical strength, and color tone for the devolvement of autopolymerizing resin with antimicrobial properties. As observed, resin-Mont and resin-NPS were capable of the sustained release of CPC for 14 d, and a higher amount of CPC was released compared to that of resin-CPC. Additionally, resin-Mont and resin-NPS could reuptake CPC. Moreover, the antimicrobial studies demonstrated that resin-Mont and resin-NPS could release effective amounts of CPC against Streptococcus mutans for 14 d and 7 d after reuptake, respectively. Compared to resin-CPC, resin-Mont exhibited a higher sustained release of CPC in all periods, both in the initial sustained release and after reuptake. However, the mechanical strength decreased with the addition of Mont and NPS, with a 36% reduction observed in flexural strength for resin-Mont and 25% for resin-NPS. The application of these results to the resin portion of the orthodontic appliances can prevent bacterial growth on the surface, as well as on the interior, of the appliances and mitigate the inflammation of the mucosa. Full article
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15 pages, 9937 KiB  
Article
Rapidly Dissolving Microneedles for the Delivery of Steroid-Loaded Nanoparticles Intended for the Treatment of Inflammatory Skin Diseases
by Hala Dawud and Aiman Abu Ammar
Pharmaceutics 2023, 15(2), 526; https://doi.org/10.3390/pharmaceutics15020526 - 04 Feb 2023
Cited by 12 | Viewed by 3489
Abstract
Drug delivery through the skin has immense advantages compared to other routes of administration and offers an optimal way to treat inflammatory skin diseases, where corticosteroids are the cornerstone of topical therapy. Still, their therapeutic efficiency is limited due to inadequate skin permeability, [...] Read more.
Drug delivery through the skin has immense advantages compared to other routes of administration and offers an optimal way to treat inflammatory skin diseases, where corticosteroids are the cornerstone of topical therapy. Still, their therapeutic efficiency is limited due to inadequate skin permeability, potential side effects, and reduced patient compliance. To overcome these drawbacks, we propose a drug delivery system consisting of dexamethasone (DEX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) incorporated in sodium alginate (SA) microneedles (MNs) as a minimally invasive dosage form for controlled drug release. Drug-loaded PLGA NPs were prepared by a nanoprecipitation method with a high encapsulation yield. They exhibited a controlled release pattern over 120 h. A modified vacuum-deposition micromolding method was used to load the obtained DEX-NPs into the tips of dissolving MNs. The NP-MNs showed improved insertion capabilities into the skin-simulant parafilm model and enhanced mechanical strength when tested against different static forces compared to their counterparts (SA-MNs). The results of an MN dissolution study following application to ex vivo chicken skin and agarose gel indicate that the NP-loaded segments of MNs dissolve within 15 s, in which the NPs are released into the skin. Taken together, the incorporation of DEX-NPs into SA-MNs could be a promising approach to bypass the limitations of conventional topical treatment of skin diseases, allowing for self-administration, increased patient compliance, and controlled drug release. Full article
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21 pages, 3387 KiB  
Article
Honokiol-Loaded Nanoemulsion for Glioblastoma Treatment: Statistical Optimization, Physicochemical Characterization, and an In Vitro Toxicity Assay
by Aleksandra Gostyńska, Joanna Czerniel, Joanna Kuźmińska, Jakub Brzozowski, Aleksandra Majchrzak-Celińska, Violetta Krajka-Kuźniak and Maciej Stawny
Pharmaceutics 2023, 15(2), 448; https://doi.org/10.3390/pharmaceutics15020448 - 29 Jan 2023
Cited by 9 | Viewed by 1562
Abstract
Background: Glioblastoma (GBM) is an extremely invasive and heterogenous malignant brain tumor. Despite advances in current anticancer therapy, treatment options for glioblastoma remain limited, and tumor recurrence is inevitable. Therefore, alternative therapies or new active compounds that can be used as adjuvant therapy [...] Read more.
Background: Glioblastoma (GBM) is an extremely invasive and heterogenous malignant brain tumor. Despite advances in current anticancer therapy, treatment options for glioblastoma remain limited, and tumor recurrence is inevitable. Therefore, alternative therapies or new active compounds that can be used as adjuvant therapy are needed. This study aimed to develop, optimize, and characterize honokiol-loaded nanoemulsions intended for intravenous administration in glioblastoma therapy. Methods: Honokiol-loaded nanoemulsion was developed by incorporating honokiol into Lipofundin MCT/LCT 20% using a horizontal shaker. The Box–Behnken design, coupled with response surface methodology, was used to optimize the incorporation process. The effect of the developed formulation on glioblastoma cell viability was determined using the MTT test. Long-term and short-term stress tests were performed to evaluate the effect of honokiol on the stability of the oil-in-water system and the effect of different stress factors on the stability of honokiol, respectively. Its physicochemical properties, such as MDD, PDI, ZP, OSM, pH, and loading efficiency (LE%), were determined. Results: The optimized honokiol-loaded nanoemulsion was characterized by an MDD of 201.4 (0.7) nm with a PDI of 0.07 (0.02) and a ZP of −28.5 (0.9) mV. The LE% of honokiol was above 95%, and pH and OSM were sufficient for intravenous administration. The developed formulation was characterized by good stability and a satisfactory toxicity effect of the glioblastoma cell lines. Conclusions: The honokiol-loaded nanoemulsion is a promising pharmaceutical formulation for further development in the adjuvant therapy of glioblastoma. Full article
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14 pages, 7084 KiB  
Article
Poly(Glycerol) Microparticles as Drug Delivery Vehicle for Biomedical Use
by Mehtap Sahiner, Aynur S. Yilmaz, Ramesh S. Ayyala and Nurettin Sahiner
Pharmaceutics 2023, 15(2), 384; https://doi.org/10.3390/pharmaceutics15020384 - 23 Jan 2023
Cited by 1 | Viewed by 1786
Abstract
Glycerol (Gly) is a well-known, FDA-approved molecule posing three hydroxyl groups. Since Gly is biocompatible, here, it was aimed to prepare poly(Glycerol) (p(Gly)) particles directly for the first time for the delivery of therapeutic agents. Micrometer-sized particles of p(Gly) were successfully synthesized via [...] Read more.
Glycerol (Gly) is a well-known, FDA-approved molecule posing three hydroxyl groups. Since Gly is biocompatible, here, it was aimed to prepare poly(Glycerol) (p(Gly)) particles directly for the first time for the delivery of therapeutic agents. Micrometer-sized particles of p(Gly) were successfully synthesized via the micro-emulsion method with an average size of 14.5 ± 5.6 µm. P(Gly) microparticles up to 1.0 g/mL concentrations were found biocompatible with 85 ± 1% cell viability against L929 fibroblasts. Moreover, p(Gly) microparticles were tested for hemocompatibility, and it was found that up to 1.0 mg/mL concentrations the particles were non-hemolytic with 0.4 ± 0.1% hemolysis ratios. In addition, the blood compatibility index values of the prepared p(Gly) particles were found as 95 ± 2%, indicating that these microparticles are both bio- and hemocompatible. Furthermore, Quercetin (QC) flavonoid, which possessed high antioxidant properties, was loaded into p(Gly) microparticles to demonstrate drug-carrying properties of the particles with improved bioavailability, non-toxicity, and high biocompatibility. The results of this study evidently revealed that p(Gly) particles can be directly prepared from a cost-effective and easily accessible glycerol molecule and the prepared particles exhibited good biocompatibility, hemocompatibility, and non-toxicity. Therefore, p(Gly) particles were found as promising vehicles for drug delivery systems in terms of their higher loading and release capability as well as for sustained long term release profiles. Full article
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18 pages, 3043 KiB  
Article
Interactions between DMPC Model Membranes, the Drug Naproxen, and the Saponin β-Aescin
by Pia Hägerbäumer, Friederike Gräbitz-Bräuer, Marco Annegarn, Carina Dargel, Tim Julian Stank, Thomas Bizien and Thomas Hellweg
Pharmaceutics 2023, 15(2), 379; https://doi.org/10.3390/pharmaceutics15020379 - 22 Jan 2023
Viewed by 1752
Abstract
In this study, the interplay among the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as a model membrane, the nonsteroidal anti-inflammatory drug naproxen, and the saponin β-aescin are investigated. The naproxen amount was fixed to 10 mol%, and the saponin amount varies from 0.0 [...] Read more.
In this study, the interplay among the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as a model membrane, the nonsteroidal anti-inflammatory drug naproxen, and the saponin β-aescin are investigated. The naproxen amount was fixed to 10 mol%, and the saponin amount varies from 0.0 to 1.0 mol%. Both substances are common ingredients in pharmaceutics; therefore, it is important to obtain deeper knowledge of their impact on lipid membranes. The size and properties of the DMPC model membrane upon naproxen and aescin addition were characterized with differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SAXS, WAXS), and photon correlation spectroscopy (PCS) in a temperature-dependent study. The interaction of all substances was dependent on the lipid phase state, which itself depends on the lipid’s main phase transition temperature Tm. The incorporation of naproxen and aescin distorted the lipid membrane structure and lowers Tm. Below Tm, the DMPC–naproxen–aescin mixtures showed a vesicle structure, and the insertion of naproxen and aescin influenced neither the lipid chain–chain correlation distance nor the membrane thickness. Above Tm, the insertion of both molecules instead induced the formation of correlated bilayers and a decrease in the chain–chain correlation distance. The presented data clearly confirm the interaction of naproxen and aescin with DMPC model membranes. Moreover, the incorporation of both additives into the model membranes is evidenced. Full article
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15 pages, 3669 KiB  
Article
New Biocompatible Nanohydrogels of Predefined Sizes for Complexing Nucleic Acids
by Lakshmanan Eswaran, Gila Kazimirsky and Gerardo Byk
Pharmaceutics 2023, 15(2), 332; https://doi.org/10.3390/pharmaceutics15020332 - 19 Jan 2023
Cited by 2 | Viewed by 1485
Abstract
The advent of protein expression using m-RNA applied lately for treating the COVID pandemic, and gene editing using CRISPR/Cas9 technology for introducing DNA sequences at a specific site in the genome, are milestones for the urgent need of developing new nucleic acid delivery [...] Read more.
The advent of protein expression using m-RNA applied lately for treating the COVID pandemic, and gene editing using CRISPR/Cas9 technology for introducing DNA sequences at a specific site in the genome, are milestones for the urgent need of developing new nucleic acid delivery systems with improved delivery properties especially for in vivo applications. We have designed, synthesized, and characterized novel cross-linked monodispersed nanohydrogels (NHG’s) with well-defined sizes ranging between 50–400 nm. The synthesis exploits the formation of self-assemblies generated upon heating a thermo-responsive mixture of monomers. Self-assemblies are formed and polymerized at high temperatures resulting in NHGs with sizes that are predetermined by the sizes of the intermediate self-assemblies. The obtained NHGs were chemically reduced to lead particles with highly positive zeta potential and low cell toxicity. The NHGs form complexes with DNA, and at optimal charge ratio the size of the complexes is concomitant with the size of the NHG’s. Thus, the DNA is fully embedded inside the NHGs. The new NHGs and their DNA complexes are devoid of cell toxicity which together with their tunned sizes, make them potential tools for gene delivery and foreign protein expression. Full article
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13 pages, 4638 KiB  
Article
Nano-Spray-Dried Levocetirizine Dihydrochloride with Mucoadhesive Carriers and Cyclodextrins for Nasal Administration
by Mirella Mirankó, Judit Tóth, Csilla Bartos, Rita Ambrus and Tivadar Feczkó
Pharmaceutics 2023, 15(2), 317; https://doi.org/10.3390/pharmaceutics15020317 - 18 Jan 2023
Cited by 2 | Viewed by 1734
Abstract
Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was nano-spray-dried using three mucoadhesive polymers and four cyclodextrin species to form composite powders for nasal administration. The product was [...] Read more.
Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was nano-spray-dried using three mucoadhesive polymers and four cyclodextrin species to form composite powders for nasal administration. The product was composed of hydroxypropyl methylcellulose polymer, including LC as a zwitterion, after neutralization by NaOH, and XRD investigations verified its amorphous state. This and a sulfobutylated-beta-cyclodextrin sodium salt-containing sample showed crystal peaks due to NaCl content as products of the neutralization reaction in the solutions before drying. The average particle size of the spherical microparticles was between 2.42 and 3.44 µm, except for those containing a polyvinyl alcohol excipient, which were characterized by a medium diameter of 29.80 µm. The drug was completely and immediately liberated from all the samples at pH 5.6 and 32 °C; i.e., the carriers did not change the good dissolution behavior of LC. A permeability test was carried out by dipping the synthetic cellulose ester membrane in isopropyl myristate using modified horizontal diffusion cells. The spray-dried powder with β-cyclodextrin showed the highest permeability (188.37 µg/cm2/h), as this additive was the least hydrophilic. Products prepared with other cyclodextrins (randomly methylated-beta-cyclodextrin, sulfobutylated-beta-cyclodextrin sodium salt and (hydroxypropyl)-beta-cyclodextrin) showed similar or slightly higher penetration abilities than LC. Other polymer excipients resulted in lower penetration of the active agent than the pure LC. Full article
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15 pages, 3082 KiB  
Article
Interaction between Pharmaceutical Drugs and Polymer-Coated Fe3O4 Magnetic Nanoparticles with Langmuir Monolayers as Cellular Membrane Models
by Sara Natalia Moya Betancourt, Candelaria Inés Cámara and Julieta Soledad Riva
Pharmaceutics 2023, 15(2), 311; https://doi.org/10.3390/pharmaceutics15020311 - 17 Jan 2023
Cited by 4 | Viewed by 1210
Abstract
Surface modification of magnetic nanoparticles (MNPs) has been reported to play a significant role in determining their interactions with cell membranes. In this research, the interactions between polymer functionalized (chitosan, CHI or diethylamino-ethyl dextran, DEAE-D) Fe3O4 MNPs, pharmaceutical drugs and [...] Read more.
Surface modification of magnetic nanoparticles (MNPs) has been reported to play a significant role in determining their interactions with cell membranes. In this research, the interactions between polymer functionalized (chitosan, CHI or diethylamino-ethyl dextran, DEAE-D) Fe3O4 MNPs, pharmaceutical drugs and model cell membranes were investigated by Langmuir isotherms and adsorption measurements. In this study, 1,2-distearoyl-sn-glycerol-3-phosphate (DSPA) phospholipid monolayers were used as cell membrane models. Insertion experiments demonstrate that diclofenac (DCFN) is not absorbed at the air–water interface, whereas triflupromazine (TFPZ) has a MIP (maximum insertion pressure) of 35 m Nm−1. The insertion of composites MNPs:TFPZ or DCFN has larger MIP values, indicating that the MNPs are adsorbed on the monolayer with the drugs. An Fe3O4@CHI:DCFN composite presented an MIP of 39 m Nm−1 and Fe3O4@DEAE-D:DCFN presented an impressive MIP of 67 mNm−1. In the case of TFPZ, the enhancement in the MIP values is also evident, being 42 mNm−1 for Fe3O4@CHI:TFPZ and 40 mNm−1 for Fe3O4@DEAE-D:DCFN composite. All MNPs:drugs composites have MIP values greater than commonly accepted membrane pressure values, indicating that MNPs:drugs can penetrate a cellular membrane. The fact that the composite MNPs:drugs present greater MIP values than separated compounds indicates that polymer-coated MNPs can act as good drug delivery systems. Full article
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17 pages, 2515 KiB  
Article
Antiadherent AgBDC Metal–Organic Framework Coating for Escherichia coli Biofilm Inhibition
by Ana Arenas-Vivo, Vanessa Celis Arias, Georgiana Amariei, Roberto Rosal, Isabel Izquierdo-Barba, Tania Hidalgo, María Vallet-Regí, Hiram I. Beltrán, Sandra Loera-Serna and Patricia Horcajada
Pharmaceutics 2023, 15(1), 301; https://doi.org/10.3390/pharmaceutics15010301 - 16 Jan 2023
Cited by 3 | Viewed by 2379
Abstract
Surface microbial colonization and its potential biofilm formation are currently a major unsolved problem, causing almost 75% of human infectious diseases. Pathogenic biofilms are capable of surviving high antibiotic doses, resulting in inefficient treatments and, subsequently, raised infection prevalence rates. Antibacterial coatings have [...] Read more.
Surface microbial colonization and its potential biofilm formation are currently a major unsolved problem, causing almost 75% of human infectious diseases. Pathogenic biofilms are capable of surviving high antibiotic doses, resulting in inefficient treatments and, subsequently, raised infection prevalence rates. Antibacterial coatings have become a promising strategy against the biofilm formation in biomedical devices due to their biocidal activity without compromising the bulk material. Here, we propose for the first time a silver-based metal–organic framework (MOF; here denoted AgBDC) showing original antifouling properties able to suppress not only the initial bacterial adhesion, but also the potential surface contamination. Firstly, the AgBDC stability (colloidal, structural and chemical) was confirmed under bacteria culture conditions by using agar diffusion and colony counting assays, evidencing its biocide effect against the challenging E. coli, one of the main representative indicators of Gram-negative resistance bacteria. Then, this material was shaped as homogeneous spin-coated AgBDC thin film, investigating its antifouling and biocide features using a combination of complementary procedures such as colony counting, optical density or confocal scanning microscopy, which allowed to visualize for the first time the biofilm impact generated by MOFs via a specific fluorochrome, calcofluor. Full article
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22 pages, 2946 KiB  
Article
Synthesis and Characterization of Innovative Microgels Based on Polyacrylic Acid and Microalgae Cell Wall and Their Potential as Antigen Delivery Vehicles
by Ileana García-Silva, Miguel Olvera-Sosa, Benita Ortega-Berlanga, Víctor Ruíz-Rodríguez, Gabriela Palestino and Sergio Rosales-Mendoza
Pharmaceutics 2023, 15(1), 133; https://doi.org/10.3390/pharmaceutics15010133 - 30 Dec 2022
Cited by 3 | Viewed by 1315
Abstract
In this study, hybrid polyacrylic acid and Schizochytrium sp. microalgae (PAA/Schizo) microgels were synthesized by inverse emulsion assisted by ultrasound using the cell wall fraction as crosslinker. Physicochemical characterization of PAA/Schizo microgels revealed polymeric spherical particles (288 ± 39 nm) and were deemed [...] Read more.
In this study, hybrid polyacrylic acid and Schizochytrium sp. microalgae (PAA/Schizo) microgels were synthesized by inverse emulsion assisted by ultrasound using the cell wall fraction as crosslinker. Physicochemical characterization of PAA/Schizo microgels revealed polymeric spherical particles (288 ± 39 nm) and were deemed stable and negatively charged. The produced microgels are not inherently toxic as cell viability was sustained above 80% when mice splenocytes were exposed to concentrations ranging 10–900 µg/mL. PAA/Schizo microgels were evaluated as antigen delivery nanovehicle by adsorbing bovine serum albumin (BSA); with a loading efficiency of 72% and loading capacity of 362 µg/mg. Overall, intranasally-immunized BALB/c mice showed null IgG or IgA responses against PAA/Schizo microgel-BSA, whereas soluble BSA induced significant humoral responses in systemic and mucosal compartments. Splenocytes proliferation assay upon BSA stimulus revealed positive CD4+ T cells-proliferation response in PAA/Schizo microgels-BSA group. Thus, PAA/Schizo microgels constitute functional antigen delivery vehicles of simple and ecofriendly synthesis. Moreover, the use of cell wall fraction as cross-linker agent provides an alternative use for the generation of high-value products using residual algae biomass from the oil industry. Our data suggests that the PAA/Schizo microgels are potential antigen delivery vehicles for immunotherapy development. Full article
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16 pages, 2079 KiB  
Article
Effect of Organomontmorillonite-Cloisite® 20A Incorporation on the Structural and Drug Release Properties of Ureasil–PEO Hybrid
by Celso R. N. Jesus, Eduardo F. Molina, Ricardo de Oliveira, Sandra H. Pulcinelli and Celso V. Santilli
Pharmaceutics 2023, 15(1), 33; https://doi.org/10.3390/pharmaceutics15010033 - 22 Dec 2022
Cited by 3 | Viewed by 1178
Abstract
This paper presents the influence of the presence of a modified organoclay, Cloisite® 20A (MMTA) on the structural and drug release properties of ureasil organic–inorganic hybrid. Sol–gel process was used to prepare the hybrid nanocomposites containing sodium diclofenac (DCF) at 5% wt. [...] Read more.
This paper presents the influence of the presence of a modified organoclay, Cloisite® 20A (MMTA) on the structural and drug release properties of ureasil organic–inorganic hybrid. Sol–gel process was used to prepare the hybrid nanocomposites containing sodium diclofenac (DCF) at 5% wt. The effect of the amount of MMTA incorporated into the ureasil hybrid matrix was evaluated and characterized in depth by different techniques such as X-ray diffraction (XRD), small angle X-ray scattering (SAXS), differential scanning calorimetry (DSC), and swelling properties. The influence of MMTA on ureasil nanocomposites release profile was evaluated by in situ UV–vis. The diffraction patterns of the UPEO–MMTA nanocomposites showed a synergistic contribution effect that led to an intensity increase and narrowed the diffraction peaks, evidencing a crystallite PEO growth as a function of the modified nanoclay content. The interactions between polyether chains and the hydrogenated tallow of MMTA led to an easy intercalation process, as observed in UPEO–MMTA nanocomposites containing low (1% wt) or high (20% wt) nanoclay content. The waterway (channels) created in UPEO–MMTA nanocomposites contributed to a free volume increase in the swollen network compared to UPEO without MMTA. The hypothesis of the channels created after intercalation of the PEO phase in the interlayer of MMTA containing organoammonium ions corroborates with the XRD results, swelling studies by SAXS, and release assays. Furthermore, when these clay particles were dispersed in the polymeric matrix by an intercalation process, water uptake improvement was observed, with an increased amount of DCF release. The design of ureasil-MMTA nanocomposites containing modified nanoclay endows them with tunable properties; for example, swelling degree followed by amount of controlled drug release, opening the way for more versatile biomedical applications. Full article
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17 pages, 4305 KiB  
Article
3D Printed Osteoblast–Alginate/Collagen Hydrogels Promote Survival, Proliferation and Mineralization at Low Doses of Strontium Calcium Polyphosphate
by Shebin Tharakan, Shams Khondkar, Sally Lee, Serin Ahn, Chris Mathew, Andrei Gresita, Michael Hadjiargyrou and Azhar Ilyas
Pharmaceutics 2023, 15(1), 11; https://doi.org/10.3390/pharmaceutics15010011 - 20 Dec 2022
Cited by 4 | Viewed by 1984
Abstract
The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are [...] Read more.
The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are vital elements of bone and their incorporation in composite materials has shown promising results for skeletal repair. In this study, we investigated strontium calcium polyphosphate (SCPP) doped 3D printed alginate/collagen hydrogels loaded with MC3T3-E1 osteoblasts. These cell-laden scaffolds were crosslinked with different concentrations of 1% SCPP to evaluate the effect of strontium ions on cell behavior and the biomaterial properties of the scaffolds. Through scanning electron microscopy and Raman spectroscopy, we showed that the scaffolds had a granular surface topography with the banding pattern of alginate around 1100 cm−1 and of collagen around 1430 cm−1. Our results revealed that 2 mg/mL of SCPP induced the greatest scaffold degradation after 7 days and least amount of swelling after 24 h. Exposure of osteoblasts to SCPP induced severe cytotoxic effects after 1 mg/mL. pH analysis demonstrated acidity in the presence of SCPP at a pH between 2 and 4 at 0.1, 0.3, 0.5, and 1 mg/mL, which can be buffered with cell culture medium. However, when the SCPP was added to the scaffolds, the overall pH increased indicating intrinsic activity of the scaffold to buffer the SCPP. Moreover, cell viability was observed for up to 21 days in scaffolds with early mineralization at 0.3, 0.5, and 1 mg/mL of SCPP. Overall, low doses of SCPP proved to be a potential additive in biomaterial approaches for bone tissue engineering; however, the cytotoxic effects due to its pH must be monitored closely. Full article
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22 pages, 4009 KiB  
Article
Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes
by Elmira A. Vasilieva, Darya A. Kuznetsova, Farida G. Valeeva, Denis M. Kuznetsov, Andrey V. Zakharov, Syumbelya K. Amerhanova, Alexandra D. Voloshina, Irina V. Zueva, Konstantin A. Petrov and Lucia Ya. Zakharova
Pharmaceutics 2022, 14(12), 2846; https://doi.org/10.3390/pharmaceutics14122846 - 19 Dec 2022
Cited by 8 | Viewed by 1776
Abstract
Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular [...] Read more.
Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular weights, and its arginine derivative was developed and optimized. The use of the polymer modification led to an increase in the encapsulation efficiency toward rhodamine B (RhB; ~85%) and 2-PAM (~60%) by 20% compared to conventional liposomes. The formation of monodispersed and stable nanosized particles with a hydrodynamic diameter of up to 130 nm was shown using dynamic light scattering. The addition of the polymers recharged the liposome surface (from −15 mV to +20 mV), which demonstrates the successful deposition of Cs on the vesicles. In vitro spectrophotometric analysis showed a slow release of substrates (RhB and 2-PAM) from the nanocontainers, while the concentration and Cs type did not significantly affect the chitosome permeability. Flow cytometry and fluorescence microscopy qualitatively and quantitatively demonstrated the penetration of the developed chitosomes into normal Chang liver and M-HeLa cervical cancer cells. At the final stage, the ability of the formulated 2-PAM to reactivate brain AChE was assessed in a model of paraoxon-induced poisoning in an in vivo test. Intranasal administration of 2-PAM-containing chitosomes allows it to reach the degree of enzyme reactivation up to 35 ± 4%. Full article
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23 pages, 5814 KiB  
Article
Influence of the Alcohols on the ZnO Synthesis and Its Properties: The Photocatalytic and Antimicrobial Activities
by Ludmila Motelica, Bogdan-Stefan Vasile, Anton Ficai, Adrian-Vasile Surdu, Denisa Ficai, Ovidiu-Cristian Oprea, Ecaterina Andronescu, Dan Corneliu Jinga and Alina Maria Holban
Pharmaceutics 2022, 14(12), 2842; https://doi.org/10.3390/pharmaceutics14122842 - 18 Dec 2022
Cited by 36 | Viewed by 2676
Abstract
Zinc oxide (ZnO) nanomaterials are used in various health-related applications, from antimicrobial textiles to wound dressing composites and from sunscreens to antimicrobial packaging. Purity, surface defects, size, and morphology of the nanoparticles are the main factors that influence the antimicrobial properties. In this [...] Read more.
Zinc oxide (ZnO) nanomaterials are used in various health-related applications, from antimicrobial textiles to wound dressing composites and from sunscreens to antimicrobial packaging. Purity, surface defects, size, and morphology of the nanoparticles are the main factors that influence the antimicrobial properties. In this study, we are comparing the properties of the ZnO nanoparticles obtained by solvolysis using a series of alcohols: primary from methanol to 1-hexanol, secondary (2-propanol and 2-butanol), and tertiary (tert-butanol). While the synthesis of ZnO nanoparticles is successfully accomplished in all primary alcohols, the use of secondary or tertiary alcohols does not lead to ZnO as final product, underlining the importance of the used solvent. The shape of the obtained nanoparticles depends on the alcohol used, from quasi-spherical to rods, and consequently, different properties are reported, including photocatalytic and antimicrobial activities. In the photocatalytic study, the ZnO obtained in 1-butanol exhibited the best performance against methylene blue (MB) dye solution, attaining a degradation efficiency of 98.24%. The comparative study among a series of usual model dyes revealed that triarylmethane dyes are less susceptible to photo-degradation. The obtained ZnO nanoparticles present a strong antimicrobial activity on a broad range of microorganisms (bacterial and fungal strains), the size and shape being the important factors. This permits further tailoring for use in medical applications. Full article
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10 pages, 2786 KiB  
Article
Artificial Base-Directed In Vivo Formulation of Aptamer–Drug Conjugates with Albumin for Long Circulation and Targeted Delivery
by Yang Sun, Xinyao Geng, Yue Ma, Yu Qin, Shangjiu Hu, Yuquan Xie and Ruowen Wang
Pharmaceutics 2022, 14(12), 2781; https://doi.org/10.3390/pharmaceutics14122781 - 13 Dec 2022
Cited by 2 | Viewed by 1646
Abstract
Aptamer–drug conjugates (ApDCs) are potential targeted pharmaceutics, but their clinical applications are hampered by fast clearance in blood. Herein we report the construction of ApDCs modified with artificial base F and the study of biological activities. Two types of F-base-modified ApDCs were prepared, [...] Read more.
Aptamer–drug conjugates (ApDCs) are potential targeted pharmaceutics, but their clinical applications are hampered by fast clearance in blood. Herein we report the construction of ApDCs modified with artificial base F and the study of biological activities. Two types of F-base-modified ApDCs were prepared, Sgc8-paclitaxel by conjugation and Sgc8-gemcitabine, by automated solid-phase synthesis. In vitro experiments showed that F-base-modified ApDCs retain the specificity of the aptamer to target cells and the biological stability is improved. In vivo studies demonstrated that the circulatory time is increased by up to 55 h or longer, as the incorporated F base leads to a stable ApDC-albumin complex as the formulation for targeted delivery. Moreover, conjugated drug molecules were released efficiently and the drug (paclitaxel) concentration in the tumor site was improved. The results demonstrate that an F-base-directed ApDC-albumin complex is a potential platform for drug delivery and targeted cancer therapy. Full article
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19 pages, 11678 KiB  
Article
Mesoporous Silica Promotes Osteogenesis of Human Adipose-Derived Stem Cells Identified by a High-Throughput Microfluidic Chip Assay
by Xin Chen, Chao Wang, Min Hao, Hang Zhao, He Xia, Liyang Yu, Dong Li, Jichuan Qiu, Haijun Li, Lin Han and Yuanhua Sang
Pharmaceutics 2022, 14(12), 2730; https://doi.org/10.3390/pharmaceutics14122730 - 06 Dec 2022
Cited by 2 | Viewed by 1421
Abstract
Silicon-derived biomaterials are conducive to regulating the fate of osteo-related stem cells, while their effects on the osteogenic differentiation of human adipose-derived stem cells (hADSCs) remain inconclusive. Mesoporous silica (mSiO2) is synthesized in a facile route that exhibited the capability of [...] Read more.
Silicon-derived biomaterials are conducive to regulating the fate of osteo-related stem cells, while their effects on the osteogenic differentiation of human adipose-derived stem cells (hADSCs) remain inconclusive. Mesoporous silica (mSiO2) is synthesized in a facile route that exhibited the capability of promoting osteogenic differentiation of hADSCs. The metabolism of SiO2 in cells is proposed according to the colocalization fluorescence analysis between lysosomes and nanoparticles. The released silicon elements promote osteogenic differentiation. The detection of secretory proteins through numerous parallel experiments performed via a microfluidic chip confirms the positive effect of SiO2 on the osteogenic differentiation of hADSCs. Moreover, constructed with superparamagnetic iron oxide (Fe3O4), the magnetic nanoparticles (MNPs) of Fe3O4@mSiO2 endow the cells with magnetic resonance imaging (MRI) properties. The MNP-regulated osteogenic differentiation of autologous adipose-derived stem cells provides considerable clinical application prospects for stem cell therapy of bone tissue repair with an effective reduction in immune rejection. Full article
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15 pages, 4459 KiB  
Article
Superparamagnetic Iron Oxide Nanoparticles and Curcumin Equally Promote Neuronal Branching Morphogenesis in the Absence of Nerve Growth Factor in PC12 Cells
by Mahshid Zarei, Abolghasem Esmaeili, Ali Zarrabi and Atefeh Zarepour
Pharmaceutics 2022, 14(12), 2692; https://doi.org/10.3390/pharmaceutics14122692 - 01 Dec 2022
Cited by 5 | Viewed by 1250
Abstract
Regeneration of the damaged neurons in neurological disorders and returning their activities are two of the main purposes of neuromedicine. Combination use of specific nanoformulations with a therapeutic compound could be a good candidate for neuroregeneration applications. Accordingly, this research aims to utilize [...] Read more.
Regeneration of the damaged neurons in neurological disorders and returning their activities are two of the main purposes of neuromedicine. Combination use of specific nanoformulations with a therapeutic compound could be a good candidate for neuroregeneration applications. Accordingly, this research aims to utilize the combination of curcumin, as a neurogenesis agent, with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate their effects on PC12 cellsʹ neuronal branching morphogenesis in the absence of nerve growth factor. Therefore, the effects of each component alone and in combination form on the cytotoxicity, neurogenesis, and neural branching morphogenesis were evaluated using MTT assay, immunofluorescence staining, and inverted microscopy, respectively. Results confirmed the effectiveness of the biocompatible iron oxide nanoparticles (with a size of about 100 nm) in improving the percentage of neural branching (p < 0.01) in PC12 cells. In addition, the combination use of these nanoparticles with curcumin could enhance the effect of curcumin on neurogenesis (p < 0.01). These results suggest that SPIONs in combination with curcumin could act as an inducing factor on PC12 neurogenesis in the absence of nerve growth factor and could offer a novel therapeutic approach to the treatment of neurodegenerative diseases. Full article
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14 pages, 3318 KiB  
Article
Hybrid Polydimethylsiloxane (PDMS) Incorporated Thermogelling System for Effective Liver Cancer Treatment
by Panqin Ma, Lu Jiang, Xi Luo, Jiayun Chen, Qi Wang, Ying Chen, Enyi Ye, Xian Jun Loh, Caisheng Wu, Yun-Long Wu and Zibiao Li
Pharmaceutics 2022, 14(12), 2623; https://doi.org/10.3390/pharmaceutics14122623 - 28 Nov 2022
Viewed by 1547
Abstract
For the delivery of anticancer drugs, an injectable in situ hydrogel with thermal responsiveness and prolonged drug release capabilities shows considerable potential. Here, we present a series of thermosensitive in situ hydrogels that serve as drug delivery systems for the treatment of liver [...] Read more.
For the delivery of anticancer drugs, an injectable in situ hydrogel with thermal responsiveness and prolonged drug release capabilities shows considerable potential. Here, we present a series of thermosensitive in situ hydrogels that serve as drug delivery systems for the treatment of liver cancer. These hydrogels were created by utilizing the polydimethylsiloxane (PDMS) oligomer, polyethylene glycol (PEG) and polypropylene glycol (PPG)’s chemical cross-linking capabilities. Doxorubicin (DOX) was encapsulated in a hydrogel with a hydrophobic core and hydrophilic shell to enhance DOX solubility. Studies into the behavior of in situ produced hydrogels at the microscopic and macroscopic levels revealed that the copolymer solution exhibits a progressive shift from sol to gel as the temperature rises. The hydrogels’ chemical composition, thermal properties, rheological characteristics, gelation period, and DOX release behavior were all reported. Subcutaneous injection in mice was used to confirm the injectability. Through the in vitro release of DOX in a PBS solution that mimics the tumor microenvironment, the hydrogel’s sustained drug release behavior was confirmed. Additionally, using human hepatocellular hepatoma, the anticancer efficacy of thermogel (DEP-2@DOX) was assessed (HepG2). The carrier polymer material DEP-2 was tested for cytotoxicity using HepG2 cells and its excellent cytocompatibility was confirmed. In conclusion, these thermally responsive injectable hydrogels are prominent potential candidates as drug delivery vehicles for the treatment of hepatocellular carcinoma. Full article
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27 pages, 6090 KiB  
Article
Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells
by Vancha Harish, Devesh Tewari, Sharfuddin Mohd, Pilli Govindaiah, Malakapogu Ravindra Babu, Rajesh Kumar, Monica Gulati, Kuppusamy Gowthamarajan, SubbaRao V. Madhunapantula, Dinesh Kumar Chellappan, Gaurav Gupta, Kamal Dua, Siva Dallavalasa and Sachin Kumar Singh
Pharmaceutics 2022, 14(11), 2403; https://doi.org/10.3390/pharmaceutics14112403 - 07 Nov 2022
Cited by 9 | Viewed by 2216
Abstract
Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of [...] Read more.
Many natural products with greater therapeutic efficacy are limited to target several chronic diseases such as cancer, diabetes, and neurodegenerative diseases. Among the natural products from hops, i.e., Xanthohumol (XH), is a prenylated chalcone. The present research work focuses on the enhancement of the poor oral bioavailability and weak pharmacokinetic profile of XH. We exemplified the development of a Xanthohumol-loaded solid lipid nanoparticles (XH-SLNs) cargo system to overcome the limitations associated with its bioavailability. The XH-SLNs were prepared by a high-shear homogenization/ultrasonication method and graphical, numerical optimization was performed by using Box–Behnken Design. Optimized XH-SLNs showed PS (108.60 nm), PDI (0.22), ZP (−12.70 mV), %EE (80.20%) and an amorphous nature that was confirmed by DSC and PXRD. FE-SEM and HRTEM revealed the spherical morphology of XH-SLNs. The results of release studies were found to be 9.40% in 12 h for naive XH, whereas only 28.42% of XH was released from XH-SLNs. The slow release of drugs may be due to immobilization of XH in the lipid matrix. In vivo pharmacokinetic study was performed for the developed XH-SLNs to verify the enhancement in the bioavailability of XH than naive XH. The enhancement in the bioavailability of the XH was confirmed from an increase in Cmax (1.07-folds), AUC0-t (4.70-folds), t1/2 (6.47-folds) and MRT (6.13-folds) after loading into SLNs. The relative bioavailability of XH loaded in SLNs and naive XH was found to be 4791% and 20.80%, respectively. The cytotoxicity study of naive XH, XH-SLNs were performed using PC-3 cell lines by taking camptothecin as positive control. The results of cytotoxicity study revealed that XH-SLNs showed good cell inhibition in a sustained pattern. This work successfully demonstrated formulation of XH-SLNs with sustained release profile and improved oral bioavailability of XH with good anticancer properties against PC-3 cells. Full article
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20 pages, 3029 KiB  
Article
Development of Guar Gum-Pectin-Based Colon Targeted Solid Self-Nanoemulsifying Drug Delivery System of Xanthohumol
by Mahesh Hanmantrao, Sourabh Chaterjee, Rajan Kumar, Sukriti Vishwas, Vancha Harish, Omji Porwal, Mohammed Alrouji, Othman Alomeir, Sharif Alhajlah, Monica Gulati, Gaurav Gupta, Kamal Dua and Sachin Kumar Singh
Pharmaceutics 2022, 14(11), 2384; https://doi.org/10.3390/pharmaceutics14112384 - 05 Nov 2022
Cited by 8 | Viewed by 1831
Abstract
Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases [...] Read more.
Present study deciphers development of oral polysaccharide-based colon targeted solid self-nanoemulsifying drug delivery system (S-SNEDDS) of xanthohumol (XH). Several studies have shown that XH has anti-inflammatory and antioxidant properties, suggesting that it could be a good candidate for the treatment of colorectal diseases (CRD). Despite its potential, XH has a low aqueous solubility. As a result, its bioavailability is constrained by the dissolution rate. The liquid (L)-SNEDDS was constituted using Labrafac PG as oil, Tween 80 as surfactant and Transcutol P as co-surfactant. The L-SNEDDS was then adsorbed onto the surface of guar gum and pectin and developed into S-SNEDDS powder. Ternary phase diagram was used to optimize the process of developing L-SNEDDS. The formulation showed mean droplet size of 118.96 ± 5.94 nm and zeta potential of −19.08 ± 0.95 mV and drug loading of 94.20 ± 4.71%. Dissolution studies carried out in medium containing rat caecal contents (RCC) represented the targeted release of S-SNEDDS powder. It was observed that S-SNEDDS showed less than 10% release XH in initial 5 h and rapid release occurred between the 5th and 10th hour. Results of cytotoxicity studies revealed good cytotoxicity of XH loaded S-SNEDDS for Caco2 cells as compared to raw-XH. Full article
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15 pages, 4551 KiB  
Article
The Role of Hidden Conformers in Determination of Conformational Preferences of Mefenamic Acid by NOESY Spectroscopy
by Konstantin V. Belov, Luís A. E. Batista de Carvalho, Alexey A. Dyshin, Sergey V. Efimov and Ilya A. Khodov
Pharmaceutics 2022, 14(11), 2276; https://doi.org/10.3390/pharmaceutics14112276 - 24 Oct 2022
Cited by 12 | Viewed by 15836
Abstract
Mefenamic acid has been used as a non-steroidal anti-inflammatory drug for a long time. However, its practical use is quite limited due to a number of side effects on the intestinal organs. Conformational polymorphism provides mefenamic acid with unique properties regarding possible modifications [...] Read more.
Mefenamic acid has been used as a non-steroidal anti-inflammatory drug for a long time. However, its practical use is quite limited due to a number of side effects on the intestinal organs. Conformational polymorphism provides mefenamic acid with unique properties regarding possible modifications obtained during the micronization process, which can improve pharmacokinetics and minimize side effects. Micronization can be performed by decompression of supercritical fluids; methods such as rapid expansion of the supercritical solution have proven their efficiency. However, this group of methods is poorly applicable for compounds with low solubility, and the modification of the method using a pharmaceutically suitable co-solvent may be useful. In our case, addition of only 2 mol% dimethyl sulfoxide increased the solubility remarkably. Information on the conformational state may be critically important for carrying out micronization. In this work, structural analysis and estimate of conformational preferences of mefenamic acid in dimethyl sulfoxide-d6 (at 25 °C and 0.1 MPa) and in a mixed solvent supercritical carbon dioxide + dimethyl sulfoxide-d6 (45 °C, 9 MPa) were performed based on nuclear Overhauser effect spectroscopy. Results show changes in the conformation fractions depending on the medium used. The importance of allowing for hidden conformers in estimating the conformational state was demonstrated in the analysis. Obtained results may be useful for improving micronization parameters. Full article
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20 pages, 5267 KiB  
Article
How to Improve Solubility and Dissolution of Irbesartan by Fabricating Ternary Solid Dispersions: Optimization and In-Vitro Characterization
by Aasma Akram, Muhammad Irfan, Walaa A. Abualsunun, Deena M. Bukhary and Mohammed Alissa
Pharmaceutics 2022, 14(11), 2264; https://doi.org/10.3390/pharmaceutics14112264 - 23 Oct 2022
Cited by 8 | Viewed by 2239
Abstract
The purpose of this study is to improve the solubility and dissolution of a poorly soluble drug, Irbesartan, using solid dispersion techniques. For that purpose, different polymers such as Soluplus®, Kollidon® VA 64, Kolliphor® P 407, and Polyinylpyrrolidone (PVP-K30) [...] Read more.
The purpose of this study is to improve the solubility and dissolution of a poorly soluble drug, Irbesartan, using solid dispersion techniques. For that purpose, different polymers such as Soluplus®, Kollidon® VA 64, Kolliphor® P 407, and Polyinylpyrrolidone (PVP-K30) were used as carriers at different concentrations to prepare solid dispersion formulations through the solvent evaporation method. In order to prepare binary dispersion formulations, Soluplus® and Kollidon® VA 64 were used at drug: polymer ratios of 1:1, 1:2, 1:3, and 1:4 (w/w). Saturation solubility of the drug in the presence of used carriers was performed to investigate the quantitative increase in solubility. Dissolution studies were performed to explore the drug release behavior from the prepared dispersions. Additionally, the characterization of the prepared formulations was carried out by performing DSC, SEM, XRD, and FTIR studies. The results revealed that among binary systems, K4 formulation (Drug: Kollidon® VA 64 at ratio of 1:4 w/w) exhibited optimal performance in terms of increased solubility, drug release, and other investigated parameters. Furthermore, ternary dispersion formulations of the optimized binary formulation were prepared with two more polymers, Kolliphor® P 407 and Polyvinylpyrrolidone (PVP-K30), at (Drug: Kollidon® VA 64:ternary polymer) ratios of 1:4:1, 1:4:2, and 1:4:3 (w/w). The results showed that KPVP (TD3) exhibited the highest increase in solubility, as well as dissolution rate, among ternary solid dispersion formulations. Results of solubility enhancement by ternary solid dispersion formulations were also supported by FTIR, DSC, XRD, and SEM analysis. Conclusively, it was found that the ternary solid dispersion-based systems were more effective compared to the binary combinations in improving solubility as well as dissolution of a poorly soluble drug (Irbesartan). Full article
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19 pages, 4179 KiB  
Article
Impact of PEGylated Liposomal Doxorubicin and Carboplatin Combination on Glioblastoma
by Mohsen Ghaferi, Aun Raza, Maedeh Koohi, Warda Zahra, Azim Akbarzadeh, Hasan Ebrahimi Shahmabadi and Seyed Ebrahim Alavi
Pharmaceutics 2022, 14(10), 2183; https://doi.org/10.3390/pharmaceutics14102183 - 13 Oct 2022
Cited by 26 | Viewed by 1984
Abstract
Glioblastoma is an incurable cancer with a 5-year survival chance of less than 5%. Chemotherapy is a therapeutic approach to treating the disease; however, due to the presence of the blood–brain barrier (BBB), the probability of success is low. To overcome this issue, [...] Read more.
Glioblastoma is an incurable cancer with a 5-year survival chance of less than 5%. Chemotherapy is a therapeutic approach to treating the disease; however, due to the presence of the blood–brain barrier (BBB), the probability of success is low. To overcome this issue, nanoparticles are promising carriers for crossing the BBB and delivering drugs to the tumor. In this study, the anticancer efficacy of doxorubicin (DOX) and carboplatin (CB) loaded into polyethylene glycol (PEG)ylated liposome nanoparticles (PEG-Lip) and in treating brain cancer was evaluated in vitro and in vivo. The results demonstrated that PEG-Lip-DOX/CB with a size of 212 ± 10 nm was synthesized that could release the loaded drugs in a controlled manner, from which 56.3% of the loaded drugs were released after 52 h. In addition, PEG-Lip-DOX/CB could significantly increase the cytotoxicity effects of the drugs against rat glioma C6 cells (IC50: 8.7 and 12.9 µM for the drugs-loaded nanoparticles and DOX + CB, respectively). The in vivo results also demonstrated that PEGylated liposomes, compared to non-PEGylated liposomes (Lip) and DOX + CB, were more efficient in increasing the therapeutic effects and decreasing the side effects of the drugs, in which the survival times of the glioblastoma-bearing rats were 39, 35, and 30 days in the PEG-Lip-DOX/CB, Lip-DOX/CB, and DOX + CB receiver groups, respectively. In addition, the weight loss was found to be 8.7, 10.5, and 13%, respectively, in the groups. The results of the toxicity evaluation were also confirmed by histopathological studies. Overall, the results of this study demonstrated that the encapsulation of DOX and CB into PEG-Lip is a promising approach to improving the properties of DOX and CB in terms of their therapeutic effects and drug side effects for the treatment of glioblastoma. Full article
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20 pages, 6093 KiB  
Article
Pulsed Laser Photo-Crosslinking of Gelatin Methacryloyl Hydrogels for the Controlled Delivery of Chlorpromazine to Combat Antimicrobial Resistance
by Tatiana Tozar, Simona Nistorescu, Mihai Boni, Gratiela Gradisteanu Pircalabioru, Irina Negut and Angela Staicu
Pharmaceutics 2022, 14(10), 2121; https://doi.org/10.3390/pharmaceutics14102121 - 06 Oct 2022
Cited by 5 | Viewed by 1774
Abstract
Hydrogels are ideal candidates for the sustained local administration of antimicrobial drugs because they have customizable physicochemical properties that allow drug release kinetics to be controlled and potentially address the issue of systemic side effects. Consequently, the purpose of this study was to [...] Read more.
Hydrogels are ideal candidates for the sustained local administration of antimicrobial drugs because they have customizable physicochemical properties that allow drug release kinetics to be controlled and potentially address the issue of systemic side effects. Consequently, the purpose of this study was to use 266 nm-pulsed laser beams to photo-crosslink gelatin methacryloyl hydrogels using Irgacure 2959 as a photo-initiator to reduce the curing time and to have an online method to monitor the process, such as laser-induced fluorescence. Additionally, irradiated chlorpromazine was loaded into the hydrogels to obtain a drug delivery system with antimicrobial activity. These hydrogels were investigated by UV–Vis and FTIR absorption spectroscopy, scanning electron microscopy, and laser-induced fluorescence spectroscopy and their structural and morphological characteristics, swelling behavior, and drug release profile were obtained. As a result the morphology, swelling behavior, and drug release profile were influenced by both the energy of the laser beam and the exposure time. The optimal hydrogel was obtained after 1 min of laser irradiation for Irgacure 2959 at 0.05% w/v concentration and gelatin methacryloyl at 10% w/v concentration. The hydrogels loaded with irradiated chlorpromazine show significant antimicrobial activity against Staphylococcus aureus and MRSA bacteria and a non-cytotoxic effect against L929 fibroblast cell lines. Full article
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15 pages, 2690 KiB  
Article
Elastin-like Polypeptide Hydrogels for Tunable, Sustained Local Chemotherapy in Malignant Glioma
by Sonja Dragojevic, Lindsay Turner, Pallabi Pal, Amol V. Janorkar and Drazen Raucher
Pharmaceutics 2022, 14(10), 2072; https://doi.org/10.3390/pharmaceutics14102072 - 28 Sep 2022
Cited by 5 | Viewed by 1611
Abstract
Glioblastoma (GBM) is a primary brain tumor that carries a dismal prognosis, which is primarily attributed to tumor recurrence after surgery and resistance to chemotherapy. Since the tumor recurrence appears near the site of surgical resection, a concept of immediate and local application [...] Read more.
Glioblastoma (GBM) is a primary brain tumor that carries a dismal prognosis, which is primarily attributed to tumor recurrence after surgery and resistance to chemotherapy. Since the tumor recurrence appears near the site of surgical resection, a concept of immediate and local application of chemotherapeutic after initial tumor removal could lead to improved treatment outcome. With the ultimate goal of developing a locally-applied, injectable drug delivery vehicle for GBM treatment, we created elastin-like polypeptide (ELP) hydrogels. The ELP hydrogels can be engineered to release anti-cancer drugs over an extended period. The purpose of this study was to evaluate the biomechanical properties of ELP hydrogels, to characterize their ability to release doxorubicin over time, and to investigate, in vitro, the anti-proliferative effect of Dox-laden ELP hydrogels on GBM. Here, we present microstructural differences, swelling ratio measurements, drug release characteristics, and in vitro effects of different ELP hydrogel compositions. We found that manipulation of the ELP–collagen ratio allows for tunable drug release, that the released drug is taken up by cells, and that incubation with a small volume of ELP-Dox hydrogel drastically reduced survival and proliferation of GBM cells in vitro. These results underscore the potential of ELP hydrogels as a local delivery strategy to improve prognosis for GBM patients after tumor resection. Full article
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15 pages, 4037 KiB  
Article
Penicillin and Oxacillin Loaded on PEGylated-Graphene Oxide to Enhance the Activity of the Antibiotics against Methicillin-Resistant Staphylococcus aureus
by Mohadeseh Mohammadi Tabar, Moj Khaleghi, Elham Bidram, Atefeh Zarepour and Ali Zarrabi
Pharmaceutics 2022, 14(10), 2049; https://doi.org/10.3390/pharmaceutics14102049 - 26 Sep 2022
Cited by 2 | Viewed by 1487
Abstract
Infectious diseases are known as the second biggest cause of death worldwide, due to the development of antibiotic resistance. To overcome this problem, nanotechnology offers some promising approaches, such as drug delivery systems that can enhance drug efficiency. Herein, a Graphene Oxide-polyethylene glycol [...] Read more.
Infectious diseases are known as the second biggest cause of death worldwide, due to the development of antibiotic resistance. To overcome this problem, nanotechnology offers some promising approaches, such as drug delivery systems that can enhance drug efficiency. Herein, a Graphene Oxide-polyethylene glycol (GO-PEG) nano-platform was synthesized and penicillin and oxacillin, two antibiotics that are ineffective against Methicillin-resistant S. aureus (MRSA), were loaded on it to improve their effectiveness. The nanocomposites were characterized using FTIR, XRD, UV–Vis, FE-SEM/EDX, and Zeta potential analyses, followed by an evaluation of their antibacterial activity toward MRSA. Based on the results, drug loaded GO-PEG nanocomposites with loading efficiencies of 81% and 92% for penicillin and oxacillin, respectively, were successfully synthesized. They showed a controlled release within six days. The zeta potential of GO-PEG-oxacillin and penicillin was −13 mV and −11 mV, respectively. The composites showed much more activity against MRSA (80–85% inhibition) in comparison to GO-PEG (almost 0% inhibition) and pure antibiotics (40–45% inhibition). SEM images of MRSA treated with GO-PEG-antibiotics showed a deformation in the structure of bacterial cells, which led to the collapse of their intracellular components. These results demonstrate the effectiveness of utilizing the GO-based nanoplatforms in enhancing the antibacterial activity of the antibiotics. Full article
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15 pages, 3720 KiB  
Article
Co-Delivery of Dihydroartemisinin and Indocyanine Green by Metal-Organic Framework-Based Vehicles for Combination Treatment of Hepatic Carcinoma
by Yang Chen, Bin Wang, Wenping Chen, Tao Wang, Min Li, Zucheng Shen, Fang Wang, Jing Jia, Fenglan Li, Xiangyu Huang, Junyang Zhuang and Ning Li
Pharmaceutics 2022, 14(10), 2047; https://doi.org/10.3390/pharmaceutics14102047 - 26 Sep 2022
Cited by 6 | Viewed by 1864
Abstract
Dihydroartemisinin (DHA), a widely used antimalarial agent, has clinical potential for the treatment of hepatic carcinoma. Although chemotherapy is indispensable for tumor therapy, it is generally limited by poor solubility, low efficiency, rapid clearance, and side effects. As an emerging treatment method, photothermal [...] Read more.
Dihydroartemisinin (DHA), a widely used antimalarial agent, has clinical potential for the treatment of hepatic carcinoma. Although chemotherapy is indispensable for tumor therapy, it is generally limited by poor solubility, low efficiency, rapid clearance, and side effects. As an emerging treatment method, photothermal therapy (PTT) has many outstanding properties, but suffers from poor photostability of photosensitizer and incomplete ablation. Multimodal therapies could combine the advantages of different therapy methods to improve antitumor efficiency. Hence, we designed a nano-delivery system (ICG&DHA@ZIF-8) using zeolitic imidazolate framework-8 (ZIF-8) with a high porous rate and pH sensitivity property, to co-load DHA and indocyanine green (ICG). Dynamic light scattering and transmission electron microscopy were used to characterize the prepared nanoparticles. The photothermal conversion and drug release performances of ICG&DHA@ZIF-8 were investigated. In vitro antitumor efficacy and cellular uptake were studied. The mechanism of the combination treatment was studied by reactive oxygen species level detection and western blot assays. In vivo antitumor assays were then studied with the guidance of ex vivo imaging. The results showed that the ICG&DHA@ZIF-8 based combination therapy could efficiently kill hepatic carcinoma cells and suppress tumor growth. This research provides a potential nanodrug for the treatment of hepatic carcinoma. Full article
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15 pages, 2941 KiB  
Article
Internal Mammary Arteries as a Model to Demonstrate Restoration of the Impaired Vasodilation in Hypertension, Using Liposomal Delivery of the CYP1B1 Inhibitor, 2,3′,4,5′-Tetramethoxystilbene
by Azziza Zaabalawi, Lewis Renshall, Frances Beards, Adam P. Lightfoot, Hans Degens, Yvonne Alexander, Ragheb Hasan, Haris Bilal, Brigitte A. Graf, Lynda K. Harris and May Azzawi
Pharmaceutics 2022, 14(10), 2046; https://doi.org/10.3390/pharmaceutics14102046 - 26 Sep 2022
Viewed by 1729
Abstract
A significant number of patients with severe cardiovascular disease, undergoing coronary artery bypass grafting (CABG), present with hypertension. While internal mammary arteries (IMAs) may be a better alternative to vein grafts, their impaired vasodilator function affects their patency. Our objectives were to (1) [...] Read more.
A significant number of patients with severe cardiovascular disease, undergoing coronary artery bypass grafting (CABG), present with hypertension. While internal mammary arteries (IMAs) may be a better alternative to vein grafts, their impaired vasodilator function affects their patency. Our objectives were to (1) determine if inhibition of the cytochrome P450 enzyme CYP1B1, using liposome-encapsulated 2,3′,4,5′-tetramethoxystilbene (TMS), can potentiate vasodilation of IMAs from CABG patients, and (2) assess mechanisms involved using coronary arteries from normal rats, in an ex vivo model of hypertension. PEGylated liposomes were synthesized and loaded with TMS (mean diameter 141 ± 0.9 nm). Liposomal delivery of TMS improved its bioavailability Compared to TMS solution (0.129 ± 0.02 ng/mL vs. 0.086 ± 0.01 ng/mL at 4 h; p < 0.05). TMS-loaded liposomes alleviated attenuated endothelial-dependent acetylcholine (ACh)-induced dilation in diseased IMAs (@ACh 10−4 M: 56.9 ± 5.1%; n = 8 vs. 12.7 ± 7.8%; n = 6; p < 0.01) for TMS-loaded liposomes vs. blank liposomes, respectively. The alleviation in dilation may be due to the potent inhibition of CYP1B1 by TMS, and subsequent reduction in reactive oxygen species (ROS) moieties and stimulation of nitric oxide synthesis. In isolated rat coronary arteries exposed to a hypertensive environment, TMS-loaded liposomes potentiated nitric oxide and endothelium-derived hyperpolarization pathways via AMPK. Our findings are promising for the future development of TMS-loaded liposomes as a promising therapeutic strategy to enhance TMS bioavailability and potentiate vasodilator function in hypertension, with relevance for early and long-term treatment of CABG patients, via the sustained and localized TMS release within IMAs. Full article
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14 pages, 1138 KiB  
Article
Fabrication, In Vitro, and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing
by Anis Rehman, Muhammad Iqbal, Barkat A. Khan, Muhammad Khalid Khan, Bader Huwaimel, Sameer Alshehri, Ali H. Alamri, Rami M. Alzhrani, Deena M. Bukhary, Awaji Y. Safhi and Khaled M. Hosny
Pharmaceutics 2022, 14(9), 1971; https://doi.org/10.3390/pharmaceutics14091971 - 19 Sep 2022
Cited by 16 | Viewed by 2019
Abstract
Wounds are the most common causes of mortality all over the world. Topical drug delivery systems are more efficient in treating wounds as compared to oral delivery systems because they bypass the disadvantages of the oral route. The aim of the present study [...] Read more.
Wounds are the most common causes of mortality all over the world. Topical drug delivery systems are more efficient in treating wounds as compared to oral delivery systems because they bypass the disadvantages of the oral route. The aim of the present study was to formulate and evaluate in vitro in vivo nanoemulgels loaded with eucalyptol for wound healing. Nanoemulsions were prepared using the solvent emulsification diffusion method by mixing an aqueous phase and an oil phase, and a nanoemulgel was then fabricated by mixing nanoemulsions with a gelling agent (Carbopol 940) in a 1:1 ratio. The nanoemulgels were evaluated regarding stability, homogeneity, pH, viscosity, Fourier-transform infrared spectroscopy (FTIR), droplet size, zeta potential, polydispersity index (PDI), spreadability, drug content, in vitro drug release, and in vivo study. The optimized formulation, F5, exhibited pH values between 5 and 6, with no significant variations at different temperatures, and acceptable homogeneity and spreadability. F5 had a droplet size of 139 ± 5.8 nm, with a low polydispersity index. FTIR studies showed the compatibility of the drug with the excipients. The drug content of F5 was 94.81%. The percentage of wound contraction of the experimental, standard, and control groups were 100% ± 0.015, 98.170% ± 0.749, and 70.846% ± 0.830, respectively. Statistically, the experimental group showed a significant difference (p < 0.03) from the other two groups. The results suggest that the formulated optimized dosage showed optimum stability, and it can be considered an effective wound healing alternative. Full article
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10 pages, 2339 KiB  
Article
Biodegradation of HA and β-TCP Ceramics Regulated by T-Cells
by Zifan Zhao, Jing Zhang, Zaibo Yang and Qin Zhao
Pharmaceutics 2022, 14(9), 1962; https://doi.org/10.3390/pharmaceutics14091962 - 16 Sep 2022
Cited by 1 | Viewed by 1588
Abstract
Biodegradability is one of the most important properties of implantable bone biomaterials, which is directly related to material bioactivity and the osteogenic effect. How foreign body giant cells (FBGC) involved in the biodegradation of bone biomaterials are regulated by the immune system is [...] Read more.
Biodegradability is one of the most important properties of implantable bone biomaterials, which is directly related to material bioactivity and the osteogenic effect. How foreign body giant cells (FBGC) involved in the biodegradation of bone biomaterials are regulated by the immune system is poorly understood. Hence, this study found that β-tricalcium phosphate (β-TCP) induced more FBGCs formation in the microenvironment (p = 0.0061) accompanied by more TNFα (p = 0.0014), IFNγ (p = 0.0024), and T-cells (p = 0.0029) than hydroxyapatite (HA), resulting in better biodegradability. The final use of T-cell depletion in mice confirmed that T-cell-mediated immune responses play a decisive role in the formation of FBGCs and promote bioceramic biodegradation. This study reveals the biological mechanism of in vivo biodegradation of implantable bone tissue engineering materials from the perspective of material-immune system interaction, which complements the mechanism of T-cells’ adaptive immunity in bone immune regulation and can be used as a theoretical basis for rational optimization of implantable material properties. Full article
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14 pages, 5591 KiB  
Article
Ibrutinib Inhibits Angiogenesis and Tumorigenesis in a BTK-Independent Manner
by Jia Liu, Zhuojun Liu, Jing Zhang, Xiaofang Chen, Junge Chen, Linlin Sui and Jian Yu
Pharmaceutics 2022, 14(9), 1876; https://doi.org/10.3390/pharmaceutics14091876 - 05 Sep 2022
Cited by 4 | Viewed by 2196
Abstract
BTK inhibitor (BTKi) Ibrutinib carries an increased bleeding risk compared to more selective BTKis Acalabrutinib and Zanubrutinib, however, its impact on vascular endothelium remains unknown. In this study, we found that Ibrutinib induced stronger cytotoxic effect on endothelial cells than Zanubrutinib, however, Acalabrutinib [...] Read more.
BTK inhibitor (BTKi) Ibrutinib carries an increased bleeding risk compared to more selective BTKis Acalabrutinib and Zanubrutinib, however, its impact on vascular endothelium remains unknown. In this study, we found that Ibrutinib induced stronger cytotoxic effect on endothelial cells than Zanubrutinib, however, Acalabrutinib cytotoxicity was extremely weak. RNA-seq, followed by KEGG analysis and quantitative RT-PCR validation, was conducted to identify the differential apoptotic target genes of BTKis, leading to their distinct cytotoxic effects on endothelial cells, which showed that Ibrutinib and Zanubrutinib dramatically modulated the expression of critical apoptotic genes, GADD45B, FOS, and BCL2A1, among which FOS and GADD45B were upregulated more significantly by Ibrutinib than Zanubrutinib, however, Acalabrutinib downregulated BCL2A1 moderately and was not able to modulate the expression of FOS and GADD45B. Next, we performed in vitro angiogenesis assays and found that Ibrutinib was more able to induce endothelial dysfunction than Zanubrutinib via stimulating more BMP4 expression, however, Acalabrutinib had no such effect. Especially, the capacity of Ibrutinib to induce endothelial dysfunction can be antagonized by targeting BMP4. Accordingly, Ibrutinib, as an angiogenesis inhibitor, inhibited ovarian and breast cancer progression in vivo. Collectively, our findings addressed a novel molecular basis underlying Ibrutinib-induced endothelial cell dysfunction and suggested the potential application of Ibrutinib to treat angiogenesis-dependent cancers. Full article
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18 pages, 3876 KiB  
Article
Design, Formulation, and Evaluation of Aloe vera Gel-Based Capsaicin Transemulgel for Osteoarthritis
by Narayana Charyulu Rompicherla, Punam Joshi, Amitha Shetty, Kalvatala Sudhakar, Hawraz Ibrahim M. Amin, Yachana Mishra, Vijay Mishra, Aqel Albutti and Naif Alhumeed
Pharmaceutics 2022, 14(9), 1812; https://doi.org/10.3390/pharmaceutics14091812 - 29 Aug 2022
Cited by 6 | Viewed by 3819
Abstract
Topical treatments are a potential therapeutic option for the therapy of osteoarthritis, with significant data supporting the effectiveness and safety of topical formulation. Topical gel formulations may offer an alternative to oral formulations to relieve osteoarthritis (OA) pain while decreasing systemic exposure. Topical [...] Read more.
Topical treatments are a potential therapeutic option for the therapy of osteoarthritis, with significant data supporting the effectiveness and safety of topical formulation. Topical gel formulations may offer an alternative to oral formulations to relieve osteoarthritis (OA) pain while decreasing systemic exposure. Topical capsaicin transemulgel may represent an effective and safe alternative. The transemulgel was prepared from aqueous Aloe vera gel and Carbopol 934 with capsaicin in clove oil emulsion. The optimized transemulgel of capsaicin showed a pH of 6.1 ± 0.1 and viscosity of 15263–998 cps. Data from in vitro diffusion demonstrated improved permeability properties. The formulation caused no skin irritation when applied topically. The optimal transemulgel spreadability was found to be 20.23 g·cm/s. In vitro and ex vivo studies of the optimized formulation were performed. The skin irritant test was performed on rat skin with an optimized and marketed formulation. Both showed no irritation on the skin. The transemulgel of the capsaicin with Aloe vera gel was proven to be effective for osteoarthritis therapy. Full article
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19 pages, 4217 KiB  
Article
Impact of Kefiran Exopolysaccharide Extraction on Its Applicability for Tissue Engineering and Regenerative Medicine
by Susana Correia, Cristiana Gonçalves, Joaquim M. Oliveira, Hajer Radhouani and Rui L. Reis
Pharmaceutics 2022, 14(8), 1713; https://doi.org/10.3390/pharmaceutics14081713 - 17 Aug 2022
Cited by 3 | Viewed by 1698
Abstract
Kefiran is an exopolysaccharide produced by the microflora of kefir grains used to produce the fermented milk beverage kefir. The health-promoting and physicochemical properties of kefiran led to its exploration for a range of applications, mainly in the food industry and biomedical fields. [...] Read more.
Kefiran is an exopolysaccharide produced by the microflora of kefir grains used to produce the fermented milk beverage kefir. The health-promoting and physicochemical properties of kefiran led to its exploration for a range of applications, mainly in the food industry and biomedical fields. Aiming to explore its potential for tissue engineering and regenerative medicine (TERM) applications, the kefiran biopolymer obtained through three different extraction methodologies was fully characterized and compared. High-quality kefiran polysaccharides were recovered with suitable yield through different extraction protocols. The methods consisted of heating the kefir grains prior to recovering kefiran by centrifugation and differed mainly in the precipitation steps included before lyophilization. Then, kefiran scaffolds were successfully produced from each extract by cryogelation and freeze-drying. In all extracts, it was possible to identify the molecular structure of the kefiran polysaccharide through 1H-NMR and FTIR spectra. The kefiran from extraction 1 showed the highest molecular weight (~3000 kDa) and the best rheological properties, showing a pseudoplastic behavior; its scaffold presented the highest value of porosity (93.2% ± 2), and wall thickness (85.8 µm ± 16.3). All extracts showed thermal stability, good injectability and desirable viscoelastic properties; the developed scaffolds demonstrated mechanical stability, elastic behavior, and pore size comprised between 98–94 µm. Additionally, all kefiran products proved to be non-cytotoxic over L929 cells. The interesting structural, physicochemical, and biological properties showed by the kefiran extracts and cryogels revealed their biomedical potential and suitability for TERM applications. Full article
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33 pages, 6112 KiB  
Article
Sustainable Release of Propranolol Hydrochloride Laden with Biconjugated-Ufasomes Chitosan Hydrogel Attenuates Cisplatin-Induced Sciatic Nerve Damage in In Vitro/In Vivo Evaluation
by Yasmin M. Ahmed, Raha Orfali, Doaa S. Hamad, Mostafa E. Rateb and Hanan O. Farouk
Pharmaceutics 2022, 14(8), 1536; https://doi.org/10.3390/pharmaceutics14081536 - 23 Jul 2022
Cited by 3 | Viewed by 2786
Abstract
Peripheral nerve injuries significantly impact patients’ quality of life and poor functional recovery. Chitosan–ufasomes (CTS–UFAs) exhibit biomimetic features, making them a viable choice for developing novel transdermal delivery for neural repair. This study aimed to investigate the role of CTS–UFAs loaded with the [...] Read more.
Peripheral nerve injuries significantly impact patients’ quality of life and poor functional recovery. Chitosan–ufasomes (CTS–UFAs) exhibit biomimetic features, making them a viable choice for developing novel transdermal delivery for neural repair. This study aimed to investigate the role of CTS–UFAs loaded with the propranolol HCl (PRO) as a model drug in enhancing sciatica in cisplatin-induced sciatic nerve damage in rats. Hence, PRO–UFAs were primed, embedding either span 20 or 60 together with oleic acid and cholesterol using a thin-film hydration process based on full factorial design (24). The influence of formulation factors on UFAs’ physicochemical characteristics and the optimum formulation selection were investigated using Design-Expert® software. Based on the optimal UFA formulation, PRO–CTS–UFAs were constructed and characterized using transmission electron microscopy, stability studies, and ex vivo permeation. In vivo trials on rats with a sciatic nerve injury tested the efficacy of PRO–CTS–UFA and PRO–UFA transdermal hydrogels, PRO solution, compared to normal rats. Additionally, oxidative stress and specific apoptotic biomarkers were assessed, supported by a sciatic nerve histopathological study. PRO–UFAs and PRO–CTS–UFAs disclosed entrapment efficiency of 82.72 ± 2.33% and 85.32 ± 2.65%, a particle size of 317.22 ± 6.43 and 336.12 ± 4.9 nm, ζ potential of −62.06 ± 0.07 and 65.24 ± 0.10 mV, and accumulatively released 70.95 ± 8.14% and 64.03 ± 1.9% PRO within 6 h, respectively. Moreover, PRO–CTS–UFAs significantly restored sciatic nerve structure, inhibited the cisplatin-dependent increase in peripheral myelin 22 gene expression and MDA levels, and further re-established sciatic nerve GSH and CAT content. Furthermore, they elicited MBP re-expression, BCL-2 mild expression, and inhibited TNF-α expression. Briefly, our findings proposed that CTS–UFAs are promising to enhance PRO transdermal delivery to manage sciatic nerve damage. Full article
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19 pages, 5819 KiB  
Article
Evolutionary Trend Analysis of Research on 5-ALA Delivery and Theranostic Applications Based on a Scientometrics Study
by You Zhou, Mulan Mo, Dexu Luo, Yi Yang, Jialin Hu, Chenqing Ye, Longxiang Lin, Chuanshan Xu and Wenjie Chen
Pharmaceutics 2022, 14(7), 1477; https://doi.org/10.3390/pharmaceutics14071477 - 15 Jul 2022
Cited by 3 | Viewed by 1777
Abstract
5-aminolevulinic acid (5-ALA) has been extensively studied for its sustainability and broad-spectrum applications in medical research and theranostics, as well as other areas. It’s a precursor of protoporphyrin IX (PpIX), a sustainable endogenous and naturally-existing photosensitizer. However, to the best of our knowledge, [...] Read more.
5-aminolevulinic acid (5-ALA) has been extensively studied for its sustainability and broad-spectrum applications in medical research and theranostics, as well as other areas. It’s a precursor of protoporphyrin IX (PpIX), a sustainable endogenous and naturally-existing photosensitizer. However, to the best of our knowledge, a scientometrics study based on the scientific knowledge assay of the overall situation on 5-ALA research has not been reported so far, which would be of major importance to the relevant researchers. In this study, we collected all the research articles published in the last two decades from the Web of Science Core Collection database and employed bibliometric methods to comprehensively analyze the dataset from different perspectives using CiteSpace. A total of 1595 articles were identified. The analysis results showed that China published the largest number of articles, and SBI Pharmaceuticals Co., Ltd. was the most productive institution that sponsored several of the most productive authors. The cluster analysis and burst detections indicated that the improvement of photodynamic efficacy theranostics is the up-to-date key direction in 5-ALA research. Furthermore, we emphatically studied nanotechnology involvement in 5-ALA delivery and theranostics research. We envision that our results will be beneficial for researchers to have a panorama of and deep insights into this area, thus inspiring further exploitations, especially of the nanomaterial-based systems for 5-ALA delivery and theranostic applications. Full article
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19 pages, 3469 KiB  
Article
Synthesis and Evaluation of Small Molecule Drug Conjugates Harnessing Thioester-Linked Maytansinoids
by Chen-Fu Lo, Tai-Yu Chiu, Yu-Tzu Liu, Li-Rung Huang, Teng-Kuang Yeh, Kuan-Hsun Huang, Kuan-Liang Liu, Chia-Yu Hsu, Ming-Yu Fang, Yu-Chen Huang, Tsu-An Hsu, Chiung-Tong Chen and Lun Kelvin Tsou
Pharmaceutics 2022, 14(7), 1316; https://doi.org/10.3390/pharmaceutics14071316 - 21 Jun 2022
Cited by 2 | Viewed by 2120
Abstract
Ligand-targeting drug conjugates are a class of clinically validated biopharmaceutical drugs constructed by conjugating cytotoxic drugs with specific disease antigen targeting ligands through appropriate linkers. The integrated linker-drug motif embedded within such a system can prevent the premature release during systemic circulation, thereby [...] Read more.
Ligand-targeting drug conjugates are a class of clinically validated biopharmaceutical drugs constructed by conjugating cytotoxic drugs with specific disease antigen targeting ligands through appropriate linkers. The integrated linker-drug motif embedded within such a system can prevent the premature release during systemic circulation, thereby allowing the targeting ligand to engage with the disease antigen and selective accumulation. We have designed and synthesized new thioester-linked maytansinoid conjugates. By performing in vitro cytotoxicity, targeting ligand binding assay, and in vivo pharmacokinetic studies, we investigated the utility of this new linker-drug moiety in the small molecule drug conjugate (SMDC) system. In particular, we conjugated the thioester-linked maytansinoids to the phosphatidylserine-targeting small molecule zinc dipicolylamine and showed that Zn8_DM1 induced tumor regression in the HCC1806 triple-negative breast cancer xenograft model. Moreover, in a spontaneous sorafenib-resistant liver cancer model, Zn8_DM1 exhibited potent antitumor growth efficacy. From quantitative mRNA analysis of Zn8_DM1 treated-tumor tissues, we observed the elevation of gene expressions associated with a “hot inflamed tumor” state. With the identification and validation of a plethora of cancer-associated antigens in the “omics” era, this work provided the insight that antibody- or small molecule-based targeting ligands can be conjugated similarly to generate new ligand-targeting drug conjugates. Full article
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16 pages, 6604 KiB  
Article
Nobiletin as a Neuroprotectant against NMDA Receptors: An In Silico Approach
by Sadaf Jahan, Neeru Singh Redhu, Arif Jamal Siddiqui, Danish Iqbal, Johra Khan, Saeed Banawas, Mohammed Alaidarous, Bader Alshehri, Shabir Ahmad Mir, Mohd Adnan and Aditya Bhushan Pant
Pharmaceutics 2022, 14(6), 1123; https://doi.org/10.3390/pharmaceutics14061123 - 25 May 2022
Cited by 8 | Viewed by 2094
Abstract
Excitotoxicity is a type of neurodegenerative disorder. It caused by excessive glutamate receptor activation, which leads to neuronal malfunction and fatality. The N-methyl-D-aspartate (NMDA) receptors are found in glutamatergic neurons, and their excessive activation is primarily responsible for excitotoxicity. They are activated by [...] Read more.
Excitotoxicity is a type of neurodegenerative disorder. It caused by excessive glutamate receptor activation, which leads to neuronal malfunction and fatality. The N-methyl-D-aspartate (NMDA) receptors are found in glutamatergic neurons, and their excessive activation is primarily responsible for excitotoxicity. They are activated by both glutamate binding and postsynaptic depolarization, facilitating Ca2+ entry upon activation. Therefore, they are now widely acknowledged as being essential targets for excitotoxicity issues. Molecular docking and molecular dynamics (MD) simulation analyses have demonstrated that nobiletin efficiently targets the binding pocket of the NMDA receptor protein and exhibits stable dynamic behavior at the binding site. In this study, five potential neuroprotectants, nobiletin, silibinin, ononin, ginkgolide B, and epigallocatechin gallate (EGCG), were screened against the glutamate NMDA receptors in humans via computational methods. An in silico ADMET study was also performed, to predict the pharmacokinetics and toxicity profile for the expression of good drug-like behavior and a non-toxic nature. It was revealed that nobiletin fulfills the criteria for all of the drug-likeness rules (Veber, Lipinski, Ghose, Muegge, and Egan) and has neither PAINS nor structural alerts (Brenks). In conclusion, nobiletin demonstrated a possible promising neuroprotectant activities compared to other selected phytochemicals. Further, it can be evaluated in the laboratory for promising therapeutic approaches for in vitro and in vivo studies. Full article
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12 pages, 2971 KiB  
Article
Development of an LNP-Encapsulated mRNA-RBD Vaccine against SARS-CoV-2 and Its Variants
by Cong Liu, Nino Rcheulishvili, Zhigao Shen, Dimitri Papukashvili, Fengfei Xie, Ziqian Wang, Xingyun Wang, Yunjiao He and Peng George Wang
Pharmaceutics 2022, 14(5), 1101; https://doi.org/10.3390/pharmaceutics14051101 - 20 May 2022
Cited by 15 | Viewed by 3421
Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly the most challenging pandemic in the current century and remains a global health emergency. As the number of COVID-19 cases in the world is on the rise and [...] Read more.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is undoubtedly the most challenging pandemic in the current century and remains a global health emergency. As the number of COVID-19 cases in the world is on the rise and variants continue to emerge, there is an urgent need for vaccines. Among all immunization approaches, mRNA vaccines have demonstrated more promising results in response to this challenge. Herein, we designed an mRNA-based vaccine encoding the receptor-binding domain (RBD) of SARS-CoV-2 encapsulated in lipid nanoparticles (LNPs). Intramuscular (i.m.) administration of the mRNA-RBD vaccine elicited broad-spectrum neutralizing antibodies and cellular responses against not only the wild-type SARS-CoV-2 virus but also Delta and Omicron variants. These results indicated that two doses of mRNA-RBD immunization conferred a strong immune response in mice against the wild-type SARS-CoV-2, while the booster dose provided a sufficient immunity against SARS-CoV-2 and its variants. Taken together, the three-dose regimen strategy of the mRNA-RBD vaccine proposed in the present study appears to be a promising reference for the development of mRNA vaccines targeting SARS-CoV-2 variants. Full article
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22 pages, 4656 KiB  
Article
Development of Jelly Loaded with Nanogel Containing Natural L-Dopa from Mucuna pruriens Seed Extract for Neuroprotection in Parkinson’s Disease
by Chuda Chittasupho, Sarin Tadtong, Suwanna Vorarat, Witcha Imaram, Sirivan Athikomkulchai, Weerasak Samee, Vipaporn Sareedenchai, Thanu Thongnopkoon, Siriporn Okonogi and Narisa Kamkaen
Pharmaceutics 2022, 14(5), 1079; https://doi.org/10.3390/pharmaceutics14051079 - 17 May 2022
Cited by 5 | Viewed by 2669
Abstract
The first line therapy of patients with Parkinson’s disease, a neurodegenerative disorder caused by the degeneration of dopaminergic neurons, is levodopa (L-dopa) given orally. Recently, the presence of natural L-dopa in the seed of Mucuna pruriens, a tropical legume in the Fabaceae [...] Read more.
The first line therapy of patients with Parkinson’s disease, a neurodegenerative disorder caused by the degeneration of dopaminergic neurons, is levodopa (L-dopa) given orally. Recently, the presence of natural L-dopa in the seed of Mucuna pruriens, a tropical legume in the Fabaceae family, was reported and it showed superior efficiency compared with synthetic L-dopa. Therefore, this study aimed to examine the phytochemical compounds, particularly for natural L-dopa, in M. pruriens seed extract and subsequently prepare a nanogel containing the extract prior to incorporation into a jelly formulation for use as a functional food in elderly patients with Parkinson’s disease. The results show that M. pruriens seed extract contains phenolic compounds, flavonoids, tannins, alkaloids, terpenoids, and saponins. The quantitative analysis performed by the HPLC method revealed that spray-dried M. pruriens seed extract contained 5.59 ± 0.21% L-dopa. M. pruriens seed extract possesses a ferric-reducing antioxidant power and shows free-radical scavenging activity, determined by DPPH and ABTS methods, suggesting a distinctive antioxidant ability of the extract. M. pruriens seed extract at 10 ng/mL did not show cytotoxicity against a neuronal cell line (SH-SY5Y cells), kidney cells (HEK293 cells), or Caco-2 cells. Nanogel of M. pruriens seed extract prepared by ionic gelation had the hydrodynamic diameter, polydispersity index and zeta potential value of 384.53 ± 11.24 nm, 0.38 ± 0.05, and −11.23 ± 1.15 mV, respectively. The transepithelial transport of L-dopa in M. pruriens seed-extract nanogel through Caco-2 cells was measured. Nanogel containing M. pruriens seed extract at the concentration of 10 ng/mL exhibited neuroprotective activity. A jelly formulation containing M. pruriens seed-extract nanogel was successfully developed. The prepared jelly exhibited the acceptable physical and microbiological stabilities upon 6 months of the stability test. The half-life of natural L-dopa in jelly were 3.2, 0.9, and 0.6 years for storage conditions at 4, 30, and 40 °C, respectively, indicating the thermal degradation of natural L-dopa. The prepared jelly containing natural L-dopa from M. pruriens seed extract with the prominent antioxidant activity is a promising option for elderly patients suffering from Parkinson’s disease. Full article
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19 pages, 4415 KiB  
Article
Regeneration of Articular Cartilage Using Membranes of Polyester Scaffolds in a Rabbit Model
by Maciej Baranowski, Monika Wasyłeczko, Anna Kosowska, Andrzej Plichta, Sebastian Kowalczyk, Andrzej Chwojnowski, Wojciech Bielecki and Jarosław Czubak
Pharmaceutics 2022, 14(5), 1016; https://doi.org/10.3390/pharmaceutics14051016 - 08 May 2022
Cited by 3 | Viewed by 1997
Abstract
One promising method for cartilage regeneration involves combining known methods, such as the microfracture technique with biomaterials, e.g., scaffolds (membranes). The most important feature of such implants is their appropriate rate of biodegradation, without the production of toxic metabolites. This study presents work [...] Read more.
One promising method for cartilage regeneration involves combining known methods, such as the microfracture technique with biomaterials, e.g., scaffolds (membranes). The most important feature of such implants is their appropriate rate of biodegradation, without the production of toxic metabolites. This study presents work on two different membranes made of polyester (L-lactide-co-ε-caprolactone-PLCA) named “PVP and “Z”. The difference between them was the use of different pore precursors—polyvinylpyrrolidone in the “PVP” scaffold and gelatin in the “Z” scaffold. These were implemented in the articular cartilage defects of rabbit knee joints (defects were created for the purpose of the study). After 8, 16, and 24 weeks of observation, and the subsequent termination of the animals, histopathology and gel permeation chromatography (GPC) examinations were performed. Statistical analysis proved that the membranes support the regeneration process. GPC testing proved that the biodegradation process is progressing exponentially, causing the membranes to degrade at the appropriate time. The surgical technique we used meets all the requirements without causing the membrane to migrate after implantation. The “PVP” membrane is better due to the fact that after 24 weeks of observation there was a statistical trend for higher histological ratings. It is also better because it is easier to implant due to its lower fragility then membrane “Z”. We conclude that the selected membranes seem to support the regeneration of articular cartilage in the rabbit model. Full article
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13 pages, 2258 KiB  
Article
Growth of MIN-6 Cells on Salmon Fibrinogen Scaffold Improves Insulin Secretion
by Ivo Laidmäe, Alar Aints and Raivo Uibo
Pharmaceutics 2022, 14(5), 941; https://doi.org/10.3390/pharmaceutics14050941 - 26 Apr 2022
Cited by 3 | Viewed by 1709
Abstract
The incidence of type I diabetes has been increasing worldwide at an annual rate of approximately 3%. One of the strategies to treat type I diabetes is islet transplantation, in which damaged β-cells are replaced with new islets. To improve β-cells’ expansion and [...] Read more.
The incidence of type I diabetes has been increasing worldwide at an annual rate of approximately 3%. One of the strategies to treat type I diabetes is islet transplantation, in which damaged β-cells are replaced with new islets. To improve β-cells’ expansion and pseudoislet formation, studies are focusing on using extracellular-matrix-resembling substrates. We evaluated the potential of salmon fibrinogen and chitosan electrospun scaffold as cell substrate for cultivating MIN-6 cells. The morphology of cells, insulin secretion and gene expression was evaluated and compared with other substrates (nanofibrous scaffold, microporous scaffold and tissue culture polystyrene). We found that all tested 3D conditions favored the pseudoislet formation of MIN-6 cells. The insulin secretion of MIN-6 cells after stimulation with high-glucose media shows approximately a 9-fold increase compared to the control group when a fibrinogen/chitosan-based electrospun scaffold was used for cultivation. The differences in insulin secretion were corroborated by differences in gene expression. The differences in insulin secretion could probably be attributed to the differences in the mechanical and/or chemical nature of the tested substrates. Full article
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19 pages, 4168 KiB  
Article
Dual Stimuli-Responsive Multifunctional Silicon Nanocarriers for Specifically Targeting Mitochondria in Human Cancer Cells
by Vy Anh Tran, Giau Van Vo, Mario A. Tan, Joon-Seo Park, Seong Soo A. An and Sang-Wha Lee
Pharmaceutics 2022, 14(4), 858; https://doi.org/10.3390/pharmaceutics14040858 - 13 Apr 2022
Cited by 8 | Viewed by 2336
Abstract
Specific targeting, selective stimuli-responsiveness, and controlled release of anticancer agents are requested for high therapeutic efficiency with a minimal adverse effect. Herein, we report the sophisticated synthesis and functionalization of fluorescent mesoporous silicon (FMPSi) nanoparticles decorated with graphene oxide (GO) nanosheets. GO-wrapped FMPSi [...] Read more.
Specific targeting, selective stimuli-responsiveness, and controlled release of anticancer agents are requested for high therapeutic efficiency with a minimal adverse effect. Herein, we report the sophisticated synthesis and functionalization of fluorescent mesoporous silicon (FMPSi) nanoparticles decorated with graphene oxide (GO) nanosheets. GO-wrapped FMPSi (FMPSi@GO) was loaded with a cisplatin (Cis) anticancer agent, and Cis-loaded FMPSi@GO (FMPSi-Cis@GO) exhibited the dual stimuli (pH and NIR)-responsiveness of controlled drug release, i.e., the drug release rate was distinctly enhanced at acidic pH 5.5 than at neutral pH 7.0 and further enhanced under NIR irradiation at acidic pH condition. Notably, dequalinium-conjugated FMPSi-Cis@GO (FMPSi-Cis@GO@DQA) demonstrated an excellent specificity for mitochondrial targeting in cancer cells without noticeable toxicity to normal human cells. Our novel silicon nanocarriers demonstrated not only stimuli (pH and NIR)-responsive controlled drug release, but also selective accumulation in the mitochondria of cancer cells and destroying them. Full article
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19 pages, 8819 KiB  
Article
Fabrication and Modelling of a Reservoir-Based Drug Delivery System for Customizable Release
by Margarethe Hauck, Jan Dittmann, Berit Zeller-Plumhoff, Roshani Madurawala, Dana Hellmold, Carolin Kubelt, Michael Synowitz, Janka Held-Feindt, Rainer Adelung, Stephan Wulfinghoff and Fabian Schütt
Pharmaceutics 2022, 14(4), 777; https://doi.org/10.3390/pharmaceutics14040777 - 02 Apr 2022
Cited by 6 | Viewed by 2367
Abstract
Localized therapy approaches have emerged as an alternative drug administration route to overcome the limitations of systemic therapies, such as the crossing of the blood–brain barrier in the case of brain tumor treatment. For this, implantable drug delivery systems (DDS) have been developed [...] Read more.
Localized therapy approaches have emerged as an alternative drug administration route to overcome the limitations of systemic therapies, such as the crossing of the blood–brain barrier in the case of brain tumor treatment. For this, implantable drug delivery systems (DDS) have been developed and extensively researched. However, to achieve an effective localized treatment, the release kinetics of DDS needs to be controlled in a defined manner, so that the concentration at the tumor site is within the therapeutic window. Thus, a DDS, with patient-specific release kinetics, is crucial for the improvement of therapy. Here, we present a computationally supported reservoir-based DDS (rDDS) development towards patient-specific release kinetics. The rDDS consists of a reservoir surrounded by a polydimethylsiloxane (PDMS) microchannel membrane. By tailoring the rDDS, in terms of membrane porosity, geometry, and drug concentration, the release profiles can be precisely adapted, with respect to the maximum concentration, release rate, and release time. The release is investigated using a model dye for varying parameters, leading to different distinct release profiles, with a maximum release of up to 60 days. Finally, a computational simulation, considering exemplary in vivo conditions (e.g., exchange of cerebrospinal fluid), is used to study the resulting drug release profiles, demonstrating the customizability of the system. The establishment of a computationally supported workflow, for development towards a patient-specific rDDS, in combination with the transfer to suitable drugs, could significantly improve the efficacy of localized therapy approaches. Full article
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14 pages, 3821 KiB  
Article
Prospective Application of Partially Digested Autologous Chondrocyte for Meniscus Tissue Engineering
by Piya-on Numpaisal, Ching-Chuan Jiang, Chang-Hsun Hsieh, Hongsen Chiang and Chung-Liang Chien
Pharmaceutics 2022, 14(3), 605; https://doi.org/10.3390/pharmaceutics14030605 - 10 Mar 2022
Cited by 1 | Viewed by 1777
Abstract
Background: Meniscus tissue engineering has yet to achieve clinical application because it requires chondrogenic induction and in vitro cell expansion. Contrarily, cartilage engineering from autologous chondrocytes has been successfully applied in one-stage surgery. If the natural chondrogenic potential of meniscus cells can be [...] Read more.
Background: Meniscus tissue engineering has yet to achieve clinical application because it requires chondrogenic induction and in vitro cell expansion. Contrarily, cartilage engineering from autologous chondrocytes has been successfully applied in one-stage surgery. If the natural chondrogenic potential of meniscus cells can be demonstrated, meniscus tissue engineering would have more value in clinical settings. Materials and Methods: In total, 10 menisci and pieces of cartilage were obtained during total knee replacements. The tissues were collected for cell isolation and expansion. Their chondrogenic properties were examined by immunohistofluorescence and gene expression analyses. Results: In native cartilage, immunofluorescence demonstrated the presence of collagen I, aggrecan, and traces of collagen I, whereas comparable staining was seen in the inner and middle meniscus. The presence of collagen I but the absence of collagen II and aggrecan were observed in the outer meniscus. In passage 2, chondrocytes showed the presence of collagen II and aggrecan, and the absence of vimentin. The vimentin and aggrecan staining were comparable in the inner and middle meniscus cells, whereas the outer cells showed only vimentin staining. In the gene expression analyses, the expressions of collagen II and aggrecan in the native chondrocyte and the inner and middle meniscus were higher than those of the cells from the outer meniscus, but they were not different in collagen I. In the passage 2 culture, chondrocytes had a higher expression of collagen II and aggrecan than the meniscus cells. Cells from the inner and middle areas had higher collagen II and aggrecan expression than those from the outer meniscus. Conclusion: Without chondrogenic induction, inner and middle meniscus cells possess a chondrogenic phenotype. Specifically, native meniscus cells exhibited more robust chondrogenic potential compared with those of the passage 2 monolayer culture. Full article
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12 pages, 2090 KiB  
Article
The Poly-Histidine Tag H6 Mediates Structural and Functional Properties of Disintegrating, Protein-Releasing Inclusion Bodies
by Julieta María Sánchez, José Vicente Carratalá, Naroa Serna, Ugutz Unzueta, Verónica Nolan, Alejandro Sánchez-Chardi, Eric Voltà-Durán, Hèctor López-Laguna, Neus Ferrer-Miralles, Antonio Villaverde and Esther Vazquez
Pharmaceutics 2022, 14(3), 602; https://doi.org/10.3390/pharmaceutics14030602 - 10 Mar 2022
Cited by 8 | Viewed by 2310
Abstract
The coordination between histidine-rich peptides and divalent cations supports the formation of nano- and micro-scale protein biomaterials, including toxic and non-toxic functional amyloids, which can be adapted as drug delivery systems. Among them, inclusion bodies (IBs) formed in recombinant bacteria have shown promise [...] Read more.
The coordination between histidine-rich peptides and divalent cations supports the formation of nano- and micro-scale protein biomaterials, including toxic and non-toxic functional amyloids, which can be adapted as drug delivery systems. Among them, inclusion bodies (IBs) formed in recombinant bacteria have shown promise as protein depots for time-sustained protein release. We have demonstrated here that the hexahistidine (H6) tag, fused to recombinant proteins, impacts both on the formation of bacterial IBs and on the conformation of the IB-forming protein, which shows a higher content of cross-beta intermolecular interactions in H6-tagged versions. Additionally, the addition of EDTA during the spontaneous disintegration of isolated IBs largely affects the protein leakage rate, again protein release being stimulated in His-tagged materials. This event depends on the number of His residues but irrespective of the location of the tag in the protein, as it occurs in either C-tagged or N-tagged proteins. The architectonic role of H6 in the formation of bacterial IBs, probably through coordination with divalent cations, offers an easy approach to manipulate protein leakage and to tailor the applicability of this material as a secretory amyloidal depot in different biomedical interfaces. In addition, the findings also offer a model to finely investigate, in a simple set-up, the mechanics of protein release from functional secretory amyloids. Full article
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22 pages, 3412 KiB  
Article
Poly ε-Caprolactone Nanoparticles for Sustained Intra-Articular Immune Modulation in Adjuvant-Induced Arthritis Rodent Model
by Ekta Singh, Riyaz Ali M. Osmani, Rinti Banerjee, Amr Selim Abu Lila, Afrasim Moin, Khaled Almansour, Hany H. Arab, Hadil Faris Alotaibi and El-Sayed Khafagy
Pharmaceutics 2022, 14(3), 519; https://doi.org/10.3390/pharmaceutics14030519 - 26 Feb 2022
Cited by 5 | Viewed by 2493
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Local therapy [...] Read more.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder with synovitis and articular pathology as its primary expositions. Leflunomide (Lfd) is an anti-rheumatic drug that is effective in the treatment of RA, but displays severe side effects upon prolonged systemic administration. Local therapy might represent a promising strategy to treat rheumatoid arthritis without eliciting systemic adverse effects. In this study, leflunomide-loaded poly(ε-caprolactone) nanoparticles (Lfd-NPs) were prepared and assessed as a local drug delivery system capable of alleviating RA-associated inflammation. Lfd-NPs were optimized using the Quality by Design (QbD) approach, applying a 32 full factorial design. In vitro drug release from NPs was examined in simulated synovial fluid. In addition, the in vivo efficacy of Lfd-NPs was evaluated in the Adjuvant Induced Arthritis (AIA) rodent model. Sustained drug release in simulated synovial fluid was observed for up to 168 h. A gradual reduction in paw volume and knee diameter was observed over the course of treatment, indicating the regression of the disease. In addition, significant reductions in serum proinflammatory markers and cytokines, including the C-reactive protein (CRP), rheumatoid factor (RF), TNF-α, IL1-β, and IL-6, were verified upon treatment with Lfd-NPs, suggesting the modulation of immune responses at the pathological site. Most importantly, no remarkable signs of toxicity were observed in Lfd-NP-treated animals. Collectively, intra-articularly administered Lfd-NPs might represent a potential therapeutic alternative to systemically administered drugs for the treatment of rheumatoid arthritis, without eliciting systemic adverse effects. Full article
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21 pages, 6620 KiB  
Article
Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer
by Qianqian Zhang, Jianwei Bao, Tijie Duan, Minxing Hu, Yuting He, Junwei Wang, Rongfeng Hu and Jihui Tang
Pharmaceutics 2022, 14(3), 510; https://doi.org/10.3390/pharmaceutics14030510 - 25 Feb 2022
Cited by 6 | Viewed by 2476
Abstract
Lung cancer is the second-most common cancer and has the highest mortality among all cancer types. Nanoparticle (NP) drug delivery systems have been used to improve the therapeutic effectiveness of lung cancer, but rapid clearance and poor targeting limit their clinical utility. Here, [...] Read more.
Lung cancer is the second-most common cancer and has the highest mortality among all cancer types. Nanoparticle (NP) drug delivery systems have been used to improve the therapeutic effectiveness of lung cancer, but rapid clearance and poor targeting limit their clinical utility. Here, we developed a nanomicelle-microsphere composite, in which doxorubicin (DOX) was loaded with spermine (Spm) modified poly (ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) micelles, and then the nanomicelles were noncovalently adsorbed on the surface of poly (lactic-co-glycolic acid) (PLGA) microspheres. The attachment was confirmed by scanning electron microscopy and confocal microscopy. In vitro cell experiments, MTT assays and intracellular uptake assays were used to demonstrate the cytotoxicity and the cellular uptake of micelles in A549 cells. In vivo biodistribution studies were conducted, an orthotopic lung cancer implantation model based on C57BL/6 mice was established, and then real-time fluorescence imaging analysis was used to study the targeted efficacy of the complex. A nanomicelle-microsphere composite was successively constructed. Moreover, Spm-modified micelles significantly enhanced cytotoxicity and displayed more efficient cellular uptake. Notably, an orthotopic lung cancer implantation model based on C57BL/6 mice was also successively established, and in vivo biodistribution studies confirmed that the complex greatly improved the distribution of DOX in the lungs and displayed notable tumor targeting. These results suggested that the nanomicelle-microsphere composite has potential application prospects in the targeted treatment of lung cancer. Full article
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18 pages, 2635 KiB  
Article
Enhancement of the Solubility and Bioavailability of Pitavastatin through a Self-Nanoemulsifying Drug Delivery System (SNEDDS)
by Mehran Ashfaq, Shahid Shah, Akhtar Rasul, Muhammad Hanif, Hafeez Ullah Khan, Ahmed Khames, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, Muhammad Yasir Ali, Mohammad A. S. Abourehab, Safirah Maheen, Omeira Iqbal, Ghulam Abbas and Amani M. El Sisi
Pharmaceutics 2022, 14(3), 482; https://doi.org/10.3390/pharmaceutics14030482 - 22 Feb 2022
Cited by 21 | Viewed by 2985
Abstract
The purpose of the study was to develop an SNEDDS to improve the solubility and bioavailability of pitavastatin. The solubility of pitavastatin in different oils, surfactants, and co-surfactants was determined and a pseudo-ternary phase diagram was constructed. The SNEDDS was characterized by zeta-sizer, [...] Read more.
The purpose of the study was to develop an SNEDDS to improve the solubility and bioavailability of pitavastatin. The solubility of pitavastatin in different oils, surfactants, and co-surfactants was determined and a pseudo-ternary phase diagram was constructed. The SNEDDS was characterized by zeta-sizer, zeta-potential, FTIR, DSC, and TGA. Release and permeation of pitavastatin from the SNEDDS was studied for 12 and 24 h, respectively. The lipolysis test, RBC lysis, effect on lipid profile, and pharmacokinetics were studied. The SPC3 formulation showed a 104 ± 1.50 nm particle size, a 0.198 polydispersity index (PDI), and a –29 zeta potential. FTIR, DSC, and TGA showed the chemical compatibility and thermal stability. The release and permeation of pitavastatin from SPC3 was 88.5 ± 2.5% and 96%, respectively. In the lipolysis test, the digestion of SPC3 yielded a high amount of pitavastatin and showed little RBC lysis. The lipid profile suggested that after 35 days of administration of the SNEDDS, there was a marked decrease in TC, LDL, and triglyceride levels. The SNEDDS of SPC3 showed an 86% viability of Caco-2 cells. Pharmacokinetics of SPC3 showed improved values of Cmax, Tmax, half-life, MRT, AUC, and AUMC compared to the reference formulation. Our study demonstrated that the SNEDDS effectively enhanced the solubility and bioavailability of a BCS class II drug. Full article
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18 pages, 5513 KiB  
Article
‘Tablet-in-Syringe’: A Novel Dosing Mechanism for Dysphagic Patients Containing Fast-Disintegrating Tablets Fabricated Using Semisolid Extrusion 3D Printing
by Pattaraporn Panraksa, Bin Zhang, Pornchai Rachtanapun, Kittisak Jantanasakulwong, Sheng Qi and Pensak Jantrawut
Pharmaceutics 2022, 14(2), 443; https://doi.org/10.3390/pharmaceutics14020443 - 18 Feb 2022
Cited by 15 | Viewed by 3682
Abstract
With the ability to fabricate personalized dosage forms and considerably shorter manufacturing time, semisolid extrusion (SSE) 3D printing has rapidly grown in popularity in recent years as a novel, versatile manufacturing method that powers a wide range of applications in the pharmaceutical field. [...] Read more.
With the ability to fabricate personalized dosage forms and considerably shorter manufacturing time, semisolid extrusion (SSE) 3D printing has rapidly grown in popularity in recent years as a novel, versatile manufacturing method that powers a wide range of applications in the pharmaceutical field. In this work, the feasibility of using SSE 3D printing to fabricate fast-disintegrating tablets (FDTs) that are pre-filled in dosing syringes was evaluated. The novel design approach, ‘tablet-in-syringe’, was aimed to ease the oral drug administration and improve the dosing accuracy for dysphagic patients. The effect of varying polymer (hydroxypropyl methylcellulose E15) concentrations and printing parameters (e.g., extrusion rate) on dimensional accuracy, physicochemical properties, disintegration time, and content uniformity of 3D-printed FDTs was studied. An overall comparison of results demonstrated that the best FDT formulation among those developed was with a polymer:drug ratio (w/w) of 1:30, printed at extrusion rate of 3.5 μL/s. The diameter of printed filaments of this formulation was observed to be similar to the nozzle diameter (22G), proving that good printing accuracy was achieved. This FDTs also had the fastest disintegration time (0.81 ± 0.14 min) and a drug (phenytoin sodium, as the model drug) content uniformity that met pharmacopeial specifications. Although the flow characteristics of the dissolved formulation still need improvement, our findings suggested that the novel ‘tablet-in-syringe’ could potentially be considered as a promising fast-disintegrating drug delivery system that can be personalized and manufactured at—or close to—the point of care for dysphagic patients using SSE. Full article
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17 pages, 2476 KiB  
Article
Precise Dosing of Pramipexole for Low-Dosed Filament Production by Hot Melt Extrusion Applying Various Feeding Methods
by Rebecca Chamberlain, Hellen Windolf, Simon Geissler, Julian Quodbach and Jörg Breitkreutz
Pharmaceutics 2022, 14(1), 216; https://doi.org/10.3390/pharmaceutics14010216 - 17 Jan 2022
Cited by 13 | Viewed by 2477
Abstract
The aim of this research was the production of low-dosed filaments via hot-melt extrusion (HME) with the model drug pramipexole for the treatment of Parkinson’s disease. The active pharmaceutical ingredient (API) and one of the polymers polyvinyl alcohol (PVA) or basic butylated methacrylate [...] Read more.
The aim of this research was the production of low-dosed filaments via hot-melt extrusion (HME) with the model drug pramipexole for the treatment of Parkinson’s disease. The active pharmaceutical ingredient (API) and one of the polymers polyvinyl alcohol (PVA) or basic butylated methacrylate copolymer (bPMMA) were fed by various dosing techniques with the aim of achieving the smallest deviation (RSD) from the target concentration of 0.1% (w/w) pramipexole. It was found that deviation from target pramipexole concentration occurred due to degradation products in bPMMA formulations. Additionally, material temperature above 120 °C led to the formation of the anhydrous form of pramipexole within the extruded filaments and need to be considered in the calculation of the recovered API. This study clearly shows that even if equilibrium state of the extrusion parameters was reached, equilibrium condition for drug content was reached relatively late in the process. In addition, the RSD calculated by the Stange–Poole equation was proposed by us to predict the final content uniformity considering the sample size of the analyzed filament. The calculated RSD, depending on sample size and drug load, can serve as upper and lower limits of variation from target concentration and can be used to evaluate the deviations of drug content in equilibrium conditions of the HME process. The lowest deviations from target concentration in equilibrium condition for drug content were obtained in filaments extruded from previously prepared granule mixtures (RSD = 6.00%, acceptance value = 12.2). These promising results can be transferred to other API–excipient combinations to produce low-dosed filaments, which can be used for, e.g., fused filament 3D printing. The introduced calculation of the RSD by Stange–Poole equation can be used for precise determination of the homogeneity of an extruded batch. Full article
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15 pages, 3500 KiB  
Article
One-Pot Preparation of Hydrophilic Polylactide Porous Scaffolds by Using Safe Solvent and Choline Taurinate Ionic Liquid
by Anna Clara De Felice, Valerio Di Lisio, Iolanda Francolini, Alessia Mariano, Antonella Piozzi, Anna Scotto d’Abusco, Elisa Sturabotti and Andrea Martinelli
Pharmaceutics 2022, 14(1), 158; https://doi.org/10.3390/pharmaceutics14010158 - 10 Jan 2022
Cited by 7 | Viewed by 1953
Abstract
Polylactides (PLAs) are a class of polymers that are very appealing in biomedical applications due to their degradability in nontoxic products, tunable structural, and mechanical properties. However, they have some drawbacks related to their high hydrophobicity, lack of functional groups able to graft [...] Read more.
Polylactides (PLAs) are a class of polymers that are very appealing in biomedical applications due to their degradability in nontoxic products, tunable structural, and mechanical properties. However, they have some drawbacks related to their high hydrophobicity, lack of functional groups able to graft bioactive molecules, and solubility in unsafe solvents. To circumvent these shortcomings, porous scaffolds for tissue engineering were prepared by vigorously mixing a solution of isotactic and atactic PLA in nontoxic ethyl acetate at 70 °C with a water solution of choline taurinate. The partial aminolysis of the polymer ester bonds by taurine –NH2 brought about the formation of PLA oligomers with surfactant activity that stabilized the water-in-oil emulsion. Upon drying, a negligible shrinking occurred, and mechanically stable porous scaffolds were obtained. By varying the polymer composition and choline taurinate concentration, it was possible to modulate the pore dimensions (30–50 µm) and mechanical properties (Young’s moduli: 1–6 MPa) of the samples. Furthermore, the grafted choline taurinate made the surface of the PLA films hydrophilic, as observed by contact angle measurements (advancing contact angle: 76°; receding contact angle: 40°–13°). The preparation method was very simple because it was based on a one-pot mild reaction that did not require an additional purification step, as all the employed chemicals were nontoxic. Full article
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Review

Jump to: Research

15 pages, 3933 KiB  
Review
Biodegradable and Sustainable Synthetic Antibodies—A Perspective
by Xiaohan Ma, Jonathan C. Knowles and Alessandro Poma
Pharmaceutics 2023, 15(5), 1440; https://doi.org/10.3390/pharmaceutics15051440 - 09 May 2023
Viewed by 1198
Abstract
Molecular imprinting technology has been around for almost a century, and we have witnessed dramatic advancements in the overall design and production of molecularly imprinted polymers (MIPs), particularly in terms of possible formats of the final products when it comes to truly resembling [...] Read more.
Molecular imprinting technology has been around for almost a century, and we have witnessed dramatic advancements in the overall design and production of molecularly imprinted polymers (MIPs), particularly in terms of possible formats of the final products when it comes to truly resembling antibody substitutes, i.e., MIP nanoparticles (MIP NPs). Nonetheless, the overall technology appears to struggle to keep up with the current global sustainability efforts, as recently elucidated in the latest comprehensive reviews, which introduced the “GREENIFICATION” concept. In this review, we will try to elucidate if these advancements in MIP nanotechnology have indeed resulted in a sustainability amelioration. We will do so by discussing the general production and purification strategies for MIP NPs, specifically from a sustainability and biodegradation perspective, also considering the final intended application and ultimate waste management. Full article
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34 pages, 4812 KiB  
Review
A Bird’s Eye View of Various Cell-Based Biomimetic Nanomedicines for the Treatment of Arthritis
by Nupur Vasdev, Bhakti Pawar, Tanisha Gupta, Mahi Mhatre and Rakesh Kumar Tekade
Pharmaceutics 2023, 15(4), 1150; https://doi.org/10.3390/pharmaceutics15041150 - 05 Apr 2023
Cited by 3 | Viewed by 2056
Abstract
Arthritis is the inflammation and tenderness of the joints because of some metabolic, infectious, or constitutional reasons. Existing arthritis treatments help in controlling the arthritic flares, but more advancement is required to cure arthritis meticulously. Biomimetic nanomedicine represents an exceptional biocompatible treatment to [...] Read more.
Arthritis is the inflammation and tenderness of the joints because of some metabolic, infectious, or constitutional reasons. Existing arthritis treatments help in controlling the arthritic flares, but more advancement is required to cure arthritis meticulously. Biomimetic nanomedicine represents an exceptional biocompatible treatment to cure arthritis by minimizing the toxic effect and eliminating the boundaries of current therapeutics. Various intracellular and extracellular pathways can be targeted by mimicking the surface, shape, or movement of the biological system to form a bioinspired or biomimetic drug delivery system. Different cell-membrane-coated biomimetic systems, and extracellular-vesicle-based and platelets-based biomimetic systems represent an emerging and efficient class of therapeutics to treat arthritis. The cell membrane from various cells such as RBC, platelets, macrophage cells, and NK cells is isolated and utilized to mimic the biological environment. Extracellular vesicles isolated from arthritis patients can be used as diagnostic tools, and plasma or MSCs-derived extracellular vesicles can be used as a therapeutic target for arthritis. Biomimetic systems guide the nanomedicines to the targeted site by hiding them from the surveillance of the immune system. Nanomedicines can be functionalized using targeted ligand and stimuli-responsive systems to reinforce their efficacy and minimize off-target effects. This review expounds on various biomimetic systems and their functionalization for the therapeutic targets of arthritis treatment, and discusses the challenges for the clinical translation of the biomimetic system. Full article
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20 pages, 3093 KiB  
Review
Sustainable Nanomaterials for Biomedical Applications
by Yuhang Zhang, Kingsley Poon, Gweneth Sofia P. Masonsong, Yogambha Ramaswamy and Gurvinder Singh
Pharmaceutics 2023, 15(3), 922; https://doi.org/10.3390/pharmaceutics15030922 - 12 Mar 2023
Cited by 8 | Viewed by 2544
Abstract
Significant progress in nanotechnology has enormously contributed to the design and development of innovative products that have transformed societal challenges related to energy, information technology, the environment, and health. A large portion of the nanomaterials developed for such applications is currently highly dependent [...] Read more.
Significant progress in nanotechnology has enormously contributed to the design and development of innovative products that have transformed societal challenges related to energy, information technology, the environment, and health. A large portion of the nanomaterials developed for such applications is currently highly dependent on energy-intensive manufacturing processes and non-renewable resources. In addition, there is a considerable lag between the rapid growth in the innovation/discovery of such unsustainable nanomaterials and their effects on the environment, human health, and climate in the long term. Therefore, there is an urgent need to design nanomaterials sustainably using renewable and natural resources with minimal impact on society. Integrating sustainability with nanotechnology can support the manufacturing of sustainable nanomaterials with optimized performance. This short review discusses challenges and a framework for designing high-performance sustainable nanomaterials. We briefly summarize the recent advances in producing sustainable nanomaterials from sustainable and natural resources and their use for various biomedical applications such as biosensing, bioimaging, drug delivery, and tissue engineering. Additionally, we provide future perspectives into the design guidelines for fabricating high-performance sustainable nanomaterials for medical applications. Full article
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19 pages, 1652 KiB  
Review
Innovation in the Development of Synthetic and Natural Ocular Drug Delivery Systems for Eye Diseases Treatment: Focusing on Drug-Loaded Ocular Inserts, Contacts, and Intraocular Lenses
by Letizia Pelusi, Domitilla Mandatori, Leonardo Mastropasqua, Luca Agnifili, Marcello Allegretti, Mario Nubile and Assunta Pandolfi
Pharmaceutics 2023, 15(2), 625; https://doi.org/10.3390/pharmaceutics15020625 - 13 Feb 2023
Cited by 5 | Viewed by 3552
Abstract
Nowadays, ocular drug delivery still remains a challenge, since the conventional dosage forms used for anterior and posterior ocular disease treatments, such as topical, systemic, and intraocular administration methods, present important limitations mainly related to the anatomical complexity of the eye. In particular, [...] Read more.
Nowadays, ocular drug delivery still remains a challenge, since the conventional dosage forms used for anterior and posterior ocular disease treatments, such as topical, systemic, and intraocular administration methods, present important limitations mainly related to the anatomical complexity of the eye. In particular, the blood–ocular barrier along with the corneal barrier, ocular surface, and lacrimal fluid secretion reduce the availability of the administered active compounds and their efficacy. These limitations have increased the need to develop safe and effective ocular delivery systems able to sustain the drug release in the interested ocular segment over time. In the last few years, thanks to the innovations in the materials and technologies employed, different ocular drug delivery systems have been developed. Therefore, this review aims to summarize the synthetic and natural drug-loaded ocular inserts, contacts, and intraocular lenses that have been recently developed, emphasizing the characteristics that make them promising for future ocular clinical applications. Full article
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21 pages, 1938 KiB  
Review
Cell-Membrane-Coated Nanoparticles for Targeted Drug Delivery to the Brain for the Treatment of Neurological Diseases
by Jianzhuang Li, Yanhao Wei, Chunlin Zhang, Rentang Bi, Yanmei Qiu, Yanan Li and Bo Hu
Pharmaceutics 2023, 15(2), 621; https://doi.org/10.3390/pharmaceutics15020621 - 13 Feb 2023
Cited by 7 | Viewed by 2554
Abstract
Neurological diseases (NDs) are a significant cause of disability and death in the global population. However, effective treatments still need to be improved for most NDs. In recent years, cell-membrane-coated nanoparticles (CMCNPs) as drug-targeting delivery systems have become a research hotspot. Such a [...] Read more.
Neurological diseases (NDs) are a significant cause of disability and death in the global population. However, effective treatments still need to be improved for most NDs. In recent years, cell-membrane-coated nanoparticles (CMCNPs) as drug-targeting delivery systems have become a research hotspot. Such a membrane-derived, nano drug-delivery system not only contributes to avoiding immune clearance but also endows nanoparticles (NPs) with various cellular and functional mimicries. This review article first provides an overview of the function and mechanism of single/hybrid cell-membrane-derived NPs. Then, we highlight the application and safety of CMCNPs in NDs. Finally, we discuss the challenges and opportunities in the field. Full article
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31 pages, 9122 KiB  
Review
A Systematic Overview of Eudragit® Based Copolymer for Smart Healthcare
by Aniket Nikam, Priya Ranjan Sahoo, Shubham Musale, Roshani R. Pagar, Ana Cláudia Paiva-Santos and Prabhanjan Shridhar Giram
Pharmaceutics 2023, 15(2), 587; https://doi.org/10.3390/pharmaceutics15020587 - 09 Feb 2023
Cited by 14 | Viewed by 5940
Abstract
Eudragit, synthesized by radical polymerization, is used for enteric coating, precise temporal release, and targeting the entire gastrointestinal system. Evonik Healthcare Germany offers different grades of Eudragit. The ratio of methacrylic acid to its methacrylate-based monomers used in the polymerization reaction defines the [...] Read more.
Eudragit, synthesized by radical polymerization, is used for enteric coating, precise temporal release, and targeting the entire gastrointestinal system. Evonik Healthcare Germany offers different grades of Eudragit. The ratio of methacrylic acid to its methacrylate-based monomers used in the polymerization reaction defines the final product’s characteristics and consequently its potential range of applications. Since 1953, these polymers have been made to use in a wide range of healthcare applications around the world. In this review, we reviewed the “known of knowns and known of unknowns” about Eudragit, from molecule to material design, its characterization, and its applications in healthcare. Full article
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31 pages, 5086 KiB  
Review
A Sustainable Solution to Skin Diseases: Ecofriendly Transdermal Patches
by Eylul Gulsen Yilmaz, Emre Ece, Özgecan Erdem, Ismail Eş and Fatih Inci
Pharmaceutics 2023, 15(2), 579; https://doi.org/10.3390/pharmaceutics15020579 - 08 Feb 2023
Cited by 9 | Viewed by 4401
Abstract
Skin is the largest epithelial surface of the human body, with a surface area of 2 m2 for the average adult human. Being an external organ, it is susceptible to more than 3000 potential skin diseases, including injury, inflammation, microbial and viral [...] Read more.
Skin is the largest epithelial surface of the human body, with a surface area of 2 m2 for the average adult human. Being an external organ, it is susceptible to more than 3000 potential skin diseases, including injury, inflammation, microbial and viral infections, and skin cancer. Due to its nature, it offers a large accessible site for administrating several medications against these diseases. The dermal and transdermal delivery of such medications are often ensured by utilizing dermal/transdermal patches or microneedles made of biocompatible and biodegradable materials. These tools provide controlled delivery of drugs to the site of action in a rapid and therapeutically effective manner with enhanced diffusivity and minimal side effects. Regrettably, they are usually fabricated using synthetic materials with possible harmful environmental effects. Manufacturing such tools using green synthesis routes and raw materials is hence essential for both ecological and economic sustainability. In this review, natural materials including chitosan/chitin, alginate, keratin, gelatin, cellulose, hyaluronic acid, pectin, and collagen utilized in designing ecofriendly patches will be explored. Their implementation in wound healing, skin cancer, inflammations, and infections will be discussed, and the significance of these studies will be evaluated with future perspectives. Full article
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22 pages, 5672 KiB  
Review
Advances in Oral Drug Delivery Systems: Challenges and Opportunities
by Jie Lou, Hongli Duan, Qin Qin, Zhipeng Teng, Fengxu Gan, Xiaofang Zhou and Xing Zhou
Pharmaceutics 2023, 15(2), 484; https://doi.org/10.3390/pharmaceutics15020484 - 01 Feb 2023
Cited by 24 | Viewed by 6951
Abstract
The oral route is the most preferred route for systemic and local drug delivery. However, the oral drug delivery system faces the harsh physiological and physicochemical environment of the gastrointestinal tract, which limits the bioavailability and targeted design of oral drug delivery system. [...] Read more.
The oral route is the most preferred route for systemic and local drug delivery. However, the oral drug delivery system faces the harsh physiological and physicochemical environment of the gastrointestinal tract, which limits the bioavailability and targeted design of oral drug delivery system. Innovative pharmaceutical approaches including nanoparticulate formulations, biomimetic drug formulations, and microfabricated devices have been explored to optimize drug targeting and bioavailability. In this review, the anatomical factors, biochemical factors, and physiology factors that influence delivering drug via oral route are discussed and recent advance in conventional and novel oral drug delivery approaches for improving drug bioavailability and targeting ability are highlighted. We also address the challenges and opportunities of oral drug delivery systems in future. Full article
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20 pages, 13759 KiB  
Review
Advances in Self-Assembled Peptides as Drug Carriers
by Yawen Gao, Lele Wang, Xue Zhang, Ziling Zhou, Xinzhu Shen, Haodong Hu, Rui Sun and Jihui Tang
Pharmaceutics 2023, 15(2), 482; https://doi.org/10.3390/pharmaceutics15020482 - 01 Feb 2023
Cited by 4 | Viewed by 2200
Abstract
In recent years, self-assembled peptide nanotechnology has attracted a great deal of attention for its ability to form various regular and ordered structures with diverse and practical functions. Self-assembled peptides can exist in different environments and are a kind of medical bio-regenerative material [...] Read more.
In recent years, self-assembled peptide nanotechnology has attracted a great deal of attention for its ability to form various regular and ordered structures with diverse and practical functions. Self-assembled peptides can exist in different environments and are a kind of medical bio-regenerative material with unique structures. These materials have good biocompatibility and controllability and can form nanoparticles, nanofibers and hydrogels to perform specific morphological functions, which are widely used in biomedical and material science fields. In this paper, the properties of self-assembled peptides, their influencing factors and the nanostructures that they form are reviewed, and the applications of self-assembled peptides as drug carriers are highlighted. Finally, the prospects and challenges for developing self-assembled peptide nanomaterials are briefly discussed. Full article
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25 pages, 3427 KiB  
Review
Aspects of Nanotechnology for COVID-19 Vaccine Development and Its Delivery Applications
by Pranav Kumar Prabhakar, Navneet Khurana, Manish Vyas, Vikas Sharma, Gaber El-Saber Batiha, Harpreet Kaur, Jashanpreet Singh, Deepak Kumar, Neha Sharma, Ajeet Kaushik and Raj Kumar
Pharmaceutics 2023, 15(2), 451; https://doi.org/10.3390/pharmaceutics15020451 - 30 Jan 2023
Cited by 5 | Viewed by 3180
Abstract
Coronavirus, a causative agent of the common cold to a much more complicated disease such as “severe acute respiratory syndrome (SARS-CoV-2), Middle East Respiratory Syndrome (MERS-CoV-2), and Coronavirus Disease 2019 (COVID-19)”, is a member of the coronaviridae family and contains a positive-sense single-stranded [...] Read more.
Coronavirus, a causative agent of the common cold to a much more complicated disease such as “severe acute respiratory syndrome (SARS-CoV-2), Middle East Respiratory Syndrome (MERS-CoV-2), and Coronavirus Disease 2019 (COVID-19)”, is a member of the coronaviridae family and contains a positive-sense single-stranded RNA of 26–32 kilobase pairs. COVID-19 has shown very high mortality and morbidity and imparted a significantly impacted socioeconomic status. There are many variants of SARS-CoV-2 that have originated from the mutation of the genetic material of the original coronavirus. This has raised the demand for efficient treatment/therapy to manage newly emerged SARS-CoV-2 infections successfully. However, different types of vaccines have been developed and administered to patients but need more attention because COVID-19 is not under complete control. In this article, currently developed nanotechnology-based vaccines are explored, such as inactivated virus vaccines, mRNA-based vaccines, DNA-based vaccines, S-protein-based vaccines, virus-vectored vaccines, etc. One of the important aspects of vaccines is their administration inside the host body wherein nanotechnology can play a very crucial role. Currently, more than 26 nanotechnology-based COVID-19 vaccine candidates are in various phases of clinical trials. Nanotechnology is one of the growing fields in drug discovery and drug delivery that can also be used for the tackling of coronavirus. Nanotechnology can be used in various ways to design and develop tools and strategies for detection, diagnosis, and therapeutic and vaccine development to protect against COVID-19. The design of instruments for speedy, precise, and sensitive diagnosis, the fabrication of potent sanitizers, the delivery of extracellular antigenic components or mRNA-based vaccines into human tissues, and the administration of antiretroviral medicines into the organism are nanotechnology-based strategies for COVID-19 management. Herein, we discuss the application of nanotechnology in COVID-19 vaccine development and the challenges and opportunities in this approach. Full article
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17 pages, 2749 KiB  
Review
Design of Functional RGD Peptide-Based Biomaterials for Tissue Engineering
by Vijay Bhooshan Kumar, Om Shanker Tiwari, Gal Finkelstein-Zuta, Sigal Rencus-Lazar and Ehud Gazit
Pharmaceutics 2023, 15(2), 345; https://doi.org/10.3390/pharmaceutics15020345 - 19 Jan 2023
Cited by 16 | Viewed by 2996
Abstract
Tissue engineering (TE) is a rapidly expanding field aimed at restoring or replacing damaged tissues. In spite of significant advancements, the implementation of TE technologies requires the development of novel, highly biocompatible three-dimensional tissue structures. In this regard, the use of peptide self-assembly [...] Read more.
Tissue engineering (TE) is a rapidly expanding field aimed at restoring or replacing damaged tissues. In spite of significant advancements, the implementation of TE technologies requires the development of novel, highly biocompatible three-dimensional tissue structures. In this regard, the use of peptide self-assembly is an effective method for developing various tissue structures and surface functionalities. Specifically, the arginine–glycine–aspartic acid (RGD) family of peptides is known to be the most prominent ligand for extracellular integrin receptors. Due to their specific expression patterns in various human tissues and their tight association with various pathophysiological conditions, RGD peptides are suitable targets for tissue regeneration and treatment as well as organ replacement. Therefore, RGD-based ligands have been widely used in biomedical research. This review article summarizes the progress made in the application of RGD for tissue and organ development. Furthermore, we examine the effect of RGD peptide structure and sequence on the efficacy of TE in clinical and preclinical studies. Additionally, we outline the recent advancement in the use of RGD functionalized biomaterials for the regeneration of various tissues, including corneal repair, artificial neovascularization, and bone TE. Full article
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21 pages, 1589 KiB  
Review
Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects
by Vladislav S. Rybchenko, Teimur K. Aliev, Anna A. Panina, Mikhail P. Kirpichnikov and Dmitry A. Dolgikh
Pharmaceutics 2023, 15(2), 336; https://doi.org/10.3390/pharmaceutics15020336 - 19 Jan 2023
Cited by 3 | Viewed by 1968
Abstract
Anti-tumor properties of several cytokines have already been investigated in multiple experiments and clinical trials. However, those studies evidenced substantial toxicities, even at low cytokine doses, and the lack of tumor specificity. These factors significantly limit clinical applications. Due to their high specificity [...] Read more.
Anti-tumor properties of several cytokines have already been investigated in multiple experiments and clinical trials. However, those studies evidenced substantial toxicities, even at low cytokine doses, and the lack of tumor specificity. These factors significantly limit clinical applications. Due to their high specificity and affinity, tumor-specific monoclonal antibodies or their antigen-binding fragments are capable of delivering fused cytokines to tumors and, therefore, of decreasing the number and severity of side effects, as well as of enhancing the therapeutic index. The present review surveys the actual antibody–cytokine fusion protein (immunocytokine) formats, their targets, mechanisms of action, and anti-tumor and other biological effects. Special attention is paid to the formats designed to prevent the off-target cytokine–receptor interactions, potentially inducing side effects. Here, we describe preclinical and clinical data and the efficacy of the antibody-mediated cytokine delivery approach, either as a single therapy or in combination with other agents. Full article
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30 pages, 4554 KiB  
Review
Microwave-Assisted Functionalization of Multi-Walled Carbon Nanotubes for Biosensor and Drug Delivery Applications
by Chanchal Kiran Thakur, Chandrabose Karthikeyan, Mariam Sami Abou-Dahech, Moawia Mohd A. M. Altabakha, Moayad Jamal Saeed Al Shahwan, Charles R. Ashby, Jr., Amit K. Tiwari, R. Jayachandra Babu and Narayana Subbiah Hari Narayana Moorthy
Pharmaceutics 2023, 15(2), 335; https://doi.org/10.3390/pharmaceutics15020335 - 19 Jan 2023
Cited by 6 | Viewed by 2598
Abstract
Microwave-assisted synthetic methods have emerged as a popular technique for surface modification and the functionalization of multi-walled carbon nanotubes (MWCNTs) for diverse drug delivery applications. Microwave-induced functionalization of MWCNTs provides a high functionalization and requires less time than conventional techniques. Microwave methods are [...] Read more.
Microwave-assisted synthetic methods have emerged as a popular technique for surface modification and the functionalization of multi-walled carbon nanotubes (MWCNTs) for diverse drug delivery applications. Microwave-induced functionalization of MWCNTs provides a high functionalization and requires less time than conventional techniques. Microwave methods are simple, fast, and effective for the covalent and noncovalent conjugation of MWCNTs with various biomolecules and polymers. The present review focuses on the synthetic and drug delivery applications of microwave irradiation techniques (MITs) for the functionalization of MWCNTs, using amino acids and other molecular frameworks containing amino groups, vitamins, proteins, epoxy moieties, metal nanoparticles, and polymers. Full article
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28 pages, 1163 KiB  
Review
The Role of Microsphere Structures in Bottom-Up Bone Tissue Engineering
by Ziyi Feng, Xin Su, Ting Wang, Xiaoting Sun, Huazhe Yang and Shu Guo
Pharmaceutics 2023, 15(2), 321; https://doi.org/10.3390/pharmaceutics15020321 - 18 Jan 2023
Viewed by 1928
Abstract
Bone defects have caused immense healthcare concerns and economic burdens throughout the world. Traditional autologous allogeneic bone grafts have many drawbacks, so the emergence of bone tissue engineering brings new hope. Bone tissue engineering is an interdisciplinary biomedical engineering method that involves scaffold [...] Read more.
Bone defects have caused immense healthcare concerns and economic burdens throughout the world. Traditional autologous allogeneic bone grafts have many drawbacks, so the emergence of bone tissue engineering brings new hope. Bone tissue engineering is an interdisciplinary biomedical engineering method that involves scaffold materials, seed cells, and “growth factors”. However, the traditional construction approach is not flexible and is unable to adapt to the specific shape of the defect, causing the cells inside the bone to be unable to receive adequate nourishment. Therefore, a simple but effective solution using the “bottom-up” method is proposed. Microspheres are structures with diameters ranging from 1 to 1000 µm that can be used as supports for cell growth, either in the form of a scaffold or in the form of a drug delivery system. Herein, we address a variety of strategies for the production of microspheres, the classification of raw materials, and drug loading, as well as analyze new strategies for the use of microspheres in bone tissue engineering. We also consider new perspectives and possible directions for future development. Full article
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48 pages, 3555 KiB  
Review
Regulation of Staphylococcus aureus Virulence and Application of Nanotherapeutics to Eradicate S. aureus Infection
by Kannappan Arunachalam, Poonguzhali Pandurangan, Chunlei Shi and Ricardo Lagoa
Pharmaceutics 2023, 15(2), 310; https://doi.org/10.3390/pharmaceutics15020310 - 17 Jan 2023
Cited by 4 | Viewed by 3507
Abstract
Staphylococcus aureus is a versatile pathogen known to cause hospital- and community-acquired, foodborne, and zoonotic infections. The clinical infections by S. aureus cause an increase in morbidity and mortality rates and treatment costs, aggravated by the emergence of drug-resistant strains. As a multi-faceted [...] Read more.
Staphylococcus aureus is a versatile pathogen known to cause hospital- and community-acquired, foodborne, and zoonotic infections. The clinical infections by S. aureus cause an increase in morbidity and mortality rates and treatment costs, aggravated by the emergence of drug-resistant strains. As a multi-faceted pathogen, it is imperative to consolidate the knowledge on its pathogenesis, including the mechanisms of virulence regulation, development of antimicrobial resistance, and biofilm formation, to make it amenable to different treatment strategies. Nanomaterials provide a suitable platform to address this challenge, with the potential to control intracellular parasitism and multidrug resistance where conventional therapies show limited efficacy. In a nutshell, the first part of this review focuses on the impact of S. aureus on human health and the role of virulence factors and biofilms during pathogenesis. The second part discusses the large diversity of nanoparticles and their applications in controlling S. aureus infections, including combination with antibiotics and phytochemicals and the incorporation of antimicrobial coatings for biomaterials. Finally, the limitations and prospects using nanomaterials are highlighted, aiming to foster the development of novel nanotechnology-driven therapies against multidrug-resistant S. aureus. Full article
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45 pages, 4188 KiB  
Review
Recent Developments in 3D Bio-Printing and Its Biomedical Applications
by Humira Assad, Arvina Assad and Ashish Kumar
Pharmaceutics 2023, 15(1), 255; https://doi.org/10.3390/pharmaceutics15010255 - 11 Jan 2023
Cited by 11 | Viewed by 2774
Abstract
The fast-developing field of 3D bio-printing has been extensively used to improve the usability and performance of scaffolds filled with cells. Over the last few decades, a variety of tissues and organs including skin, blood vessels, and hearts, etc., have all been produced [...] Read more.
The fast-developing field of 3D bio-printing has been extensively used to improve the usability and performance of scaffolds filled with cells. Over the last few decades, a variety of tissues and organs including skin, blood vessels, and hearts, etc., have all been produced in large quantities via 3D bio-printing. These tissues and organs are not only able to serve as building blocks for the ultimate goal of repair and regeneration, but they can also be utilized as in vitro models for pharmacokinetics, drug screening, and other purposes. To further 3D-printing uses in tissue engineering, research on novel, suitable biomaterials with quick cross-linking capabilities is a prerequisite. A wider variety of acceptable 3D-printed materials are still needed, as well as better printing resolution (particularly at the nanoscale range), speed, and biomaterial compatibility. The aim of this study is to provide expertise in the most prevalent and new biomaterials used in 3D bio-printing as well as an introduction to the associated approaches that are frequently considered by researchers. Furthermore, an effort has been made to convey the most pertinent implementations of 3D bio-printing processes, such as tissue regeneration, etc., by providing the most significant research together with a comprehensive list of material selection guidelines, constraints, and future prospects. Full article
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55 pages, 8762 KiB  
Review
Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment
by Ruma Rani, Parth Malik, Sunena Dhania and Tapan Kumar Mukherjee
Pharmaceutics 2023, 15(1), 227; https://doi.org/10.3390/pharmaceutics15010227 - 09 Jan 2023
Cited by 7 | Viewed by 3478
Abstract
Breast cancer (BC) currently occupies the second rank in cancer-related global female deaths. Although consistent awareness and improved diagnosis have reduced mortality in recent years, late diagnosis and resistant response still limit the therapeutic efficacy of chemotherapeutic drugs (CDs), leading to relapse with [...] Read more.
Breast cancer (BC) currently occupies the second rank in cancer-related global female deaths. Although consistent awareness and improved diagnosis have reduced mortality in recent years, late diagnosis and resistant response still limit the therapeutic efficacy of chemotherapeutic drugs (CDs), leading to relapse with consequent invasion and metastasis. Treatment with CDs is indeed well-versed but it is badly curtailed with accompanying side effects and inadequacies of site-specific drug delivery. As a result, drug carriers ensuring stealth delivery and sustained drug release with improved pharmacokinetics and biodistribution are urgently needed. Core–shell mesoporous silica nanoparticles (MSNPs) have recently been a cornerstone in this context, attributed to their high surface area, low density, robust functionalization, high drug loading capacity, size–shape-controlled functioning, and homogeneous shell architecture, enabling stealth drug delivery. Recent interest in using MSNPs as drug delivery vehicles has been due to their functionalization and size–shape-driven versatilities. With such insights, this article focuses on the preparation methods and drug delivery mechanisms of MSNPs, before discussing their emerging utility in BC treatment. The information compiled herein could consolidate the database for using inorganic nanoparticles (NPs) as BC drug delivery vehicles in terms of design, application and resolving post-therapy complications. Full article
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33 pages, 1582 KiB  
Review
Recent Advances in Genomics-Based Approaches for the Development of Intracellular Bacterial Pathogen Vaccines
by Muhammad Ajmal Khan, Aftab Amin, Awais Farid, Amin Ullah, Abdul Waris, Khyber Shinwari, Yaseen Hussain, Khalaf F. Alsharif, Khalid J. Alzahrani and Haroon Khan
Pharmaceutics 2023, 15(1), 152; https://doi.org/10.3390/pharmaceutics15010152 - 31 Dec 2022
Cited by 2 | Viewed by 2181
Abstract
Infectious diseases continue to be a leading cause of morbidity and mortality worldwide. The majority of infectious diseases are caused by intracellular pathogenic bacteria (IPB). Historically, conventional vaccination drives have helped control the pathogenesis of intracellular bacteria and the emergence of antimicrobial resistance, [...] Read more.
Infectious diseases continue to be a leading cause of morbidity and mortality worldwide. The majority of infectious diseases are caused by intracellular pathogenic bacteria (IPB). Historically, conventional vaccination drives have helped control the pathogenesis of intracellular bacteria and the emergence of antimicrobial resistance, saving millions of lives. However, in light of various limitations, many diseases that involve IPB still do not have adequate vaccines. In response to increasing demand for novel vaccine development strategies, a new area of vaccine research emerged following the advent of genomics technology, which changed the paradigm of vaccine development by utilizing the complete genomic data of microorganisms against them. It became possible to identify genes related to disease virulence, genetic patterns linked to disease virulence, as well as the genetic components that supported immunity and favorable vaccine responses. Complete genomic databases, and advancements in transcriptomics, metabolomics, structural genomics, proteomics, immunomics, pan-genomics, synthetic genomics, and population biology have allowed researchers to identify potential vaccine candidates and predict their effects in patients. New vaccines have been created against diseases for which previously there were no vaccines available, and existing vaccines have been improved. This review highlights the key issues and explores the evolution of vaccines. The increasing volume of IPB genomic data, and their application in novel genome-based techniques for vaccine development, were also examined, along with their characteristics, and the opportunities and obstacles involved. Critically, the application of genomics technology has helped researchers rapidly select and evaluate candidate antigens. Novel vaccines capable of addressing the limitations associated with conventional vaccines have been developed and pressing healthcare issues are being addressed. Full article
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15 pages, 1912 KiB  
Review
Aptamers Enhance Oncolytic Viruses’ Antitumor Efficacy
by Maya A. Dymova, Anna S. Kichkailo, Elena V. Kuligina and Vladimir A. Richter
Pharmaceutics 2023, 15(1), 151; https://doi.org/10.3390/pharmaceutics15010151 - 31 Dec 2022
Cited by 2 | Viewed by 1801
Abstract
Oncolytic viruses are highly promising for cancer treatment because they target and lyse tumor cells. These genetically engineered vectors introduce therapeutic or immunostimulatory genes into the tumor. However, viral therapy is not always safe and effective. Several problems are related to oncolytic viruses’ [...] Read more.
Oncolytic viruses are highly promising for cancer treatment because they target and lyse tumor cells. These genetically engineered vectors introduce therapeutic or immunostimulatory genes into the tumor. However, viral therapy is not always safe and effective. Several problems are related to oncolytic viruses’ targeted delivery to the tumor and immune system neutralization in the bloodstream. Cryoprotection and preventing viral particles from aggregating during storage are other critical issues. Aptamers, short RNA, or DNA oligonucleotides may help to crawl through this bottleneck. They are not immunogenic, are easily synthesized, can be chemically modified, and are not very demanding in storage conditions. It is possible to select an aptamer that specifically binds to any target cell, oncolytic virus, or molecule using the SELEX technology. This review comprehensively highlights the most important research and methodological approaches related to oncolytic viruses and nucleic acid aptamers. Here, we also analyze possible future research directions for combining these two methodologies to improve the effectiveness of cancer virotherapy. Full article
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11 pages, 1610 KiB  
Review
Standardization and Key Aspects of the Development of Whole Yeast Cell Vaccines
by Anna Jéssica Duarte Silva, Crislaine Kelly da Silva Rocha and Antonio Carlos de Freitas
Pharmaceutics 2022, 14(12), 2792; https://doi.org/10.3390/pharmaceutics14122792 - 14 Dec 2022
Cited by 2 | Viewed by 2150
Abstract
In the context of vaccine development, improving antigenic presentation is critical for the activation of specific immune responses and the success of immunization, in addition to selecting an appropriate target. In this sense, different strategies have been developed and improved. Among them is [...] Read more.
In the context of vaccine development, improving antigenic presentation is critical for the activation of specific immune responses and the success of immunization, in addition to selecting an appropriate target. In this sense, different strategies have been developed and improved. Among them is the use of yeast cells as vehicles for the delivery of recombinant antigens. These vaccines, named whole yeast vaccines (WYVs), can induce humoral and cellular immune responses, with the additional advantage of dispensing with the use of adjuvants due to the immunostimulatory properties of their cell wall components. However, there are some gaps in the methodologies for obtaining and validating recombinant strains and vaccine formulations. The standardization of these parameters is an important factor for WYVs approval by regulatory agencies and, consequently, their licensing. This review aimed to provide an overview of the main parameters to consider when developing a yeast-based vaccine, addressing some available tools, and highlighting the main variables that can influence the vaccine production process. Full article
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28 pages, 1681 KiB  
Review
Convergence of Biofabrication Technologies and Cell Therapies for Wound Healing
by Motaharesadat Hosseini, Andrew J. Dalley and Abbas Shafiee
Pharmaceutics 2022, 14(12), 2749; https://doi.org/10.3390/pharmaceutics14122749 - 08 Dec 2022
Cited by 1 | Viewed by 1781
Abstract
Background: Cell therapy holds great promise for cutaneous wound treatment but presents practical and clinical challenges, mainly related to the lack of a supportive and inductive microenvironment for cells after transplantation. Main: This review delineates the challenges and opportunities in cell therapies for [...] Read more.
Background: Cell therapy holds great promise for cutaneous wound treatment but presents practical and clinical challenges, mainly related to the lack of a supportive and inductive microenvironment for cells after transplantation. Main: This review delineates the challenges and opportunities in cell therapies for acute and chronic wounds and highlights the contribution of biofabricated matrices to skin reconstruction. The complexity of the wound healing process necessitates the development of matrices with properties comparable to the extracellular matrix in the skin for their structure and composition. Over recent years, emerging biofabrication technologies have shown a capacity for creating complex matrices. In cell therapy, multifunctional material-based matrices have benefits in enhancing cell retention and survival, reducing healing time, and preventing infection and cell transplant rejection. Additionally, they can improve the efficacy of cell therapy, owing to their potential to modulate cell behaviors and regulate spatiotemporal patterns of wound healing. Conclusion: The ongoing development of biofabrication technologies promises to deliver material-based matrices that are rich in supportive, phenotype patterning cell niches and are robust enough to provide physical protection for the cells during implantation. Full article
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49 pages, 4876 KiB  
Review
Key Parameters for the Rational Design, Synthesis, and Functionalization of Biocompatible Mesoporous Silica Nanoparticles
by Marta Florensa, Marina Llenas, Esperanza Medina-Gutiérrez, Stefania Sandoval and Gerard Tobías-Rossell
Pharmaceutics 2022, 14(12), 2703; https://doi.org/10.3390/pharmaceutics14122703 - 02 Dec 2022
Cited by 17 | Viewed by 3129
Abstract
Over the last few years, research on silica nanoparticles has rapidly increased. Particularly on mesoporous silica nanoparticles (MSNs), as nanocarriers for the treatment of various diseases because of their physicochemical properties and biocompatibility. The use of MSNs combined with therapeutic agents can provide [...] Read more.
Over the last few years, research on silica nanoparticles has rapidly increased. Particularly on mesoporous silica nanoparticles (MSNs), as nanocarriers for the treatment of various diseases because of their physicochemical properties and biocompatibility. The use of MSNs combined with therapeutic agents can provide better encapsulation and effective delivery. MSNs as nanocarriers might also be a promising tool to lower the therapeutic dosage levels and thereby to reduce undesired side effects. Researchers have explored several routes to conjugate both imaging and therapeutic agents onto MSNs, thus expanding their potential as theranostic platforms, in order to allow for the early diagnosis and treatment of diseases. This review introduces a general overview of recent advances in the field of silica nanoparticles. In particular, the review tackles the fundamental aspects of silicate materials, including a historical presentation to new silicates and then focusing on the key parameters that govern the tailored synthesis of functional MSNs. Finally, the biomedical applications of MSNs are briefly revised, along with their biocompatibility, biodistribution and degradation. This review aims to provide the reader with the tools for a rational design of biocompatible MSNs for their application in the biomedical field. Particular attention is paid to the role that the synthesis conditions have on the physicochemical properties of the resulting MSNs, which, in turn, will determine their pharmacological behavior. Several recent examples are highlighted to stress the potential that MSNs hold as drug delivery systems, for biomedical imaging, as vaccine adjuvants and as theragnostic agents. Full article
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21 pages, 4368 KiB  
Review
The Application of Black Phosphorus Nanomaterials in Bone Tissue Engineering
by Xirui Jing, Zekang Xiong, Zian Lin and Tingfang Sun
Pharmaceutics 2022, 14(12), 2634; https://doi.org/10.3390/pharmaceutics14122634 - 28 Nov 2022
Cited by 6 | Viewed by 1757
Abstract
Recently, research on and the application of nanomaterials such as graphene, carbon nanotubes, and metal–organic frameworks has become increasingly popular in tissue engineering. In 2014, a two-dimensional sheet of black phosphorus (BP) was isolated from massive BP crystals. Since then, BP has attracted [...] Read more.
Recently, research on and the application of nanomaterials such as graphene, carbon nanotubes, and metal–organic frameworks has become increasingly popular in tissue engineering. In 2014, a two-dimensional sheet of black phosphorus (BP) was isolated from massive BP crystals. Since then, BP has attracted significant attention as an emerging nanomaterial. BP possesses many advantages such as light responsiveness, electrical conductivity, degradability, and good biocompatibility. Thus, it has broad prospects in biomedical applications. Moreover, BP is composed of phosphorus, which is a key bone tissue component with good biocompatibility and osteogenic repair ability. Thereby, BP exhibits excellent advantages for application in bone tissue engineering. In this review, the structure and the physical and chemical properties of BP are described. In addition, the current applications of BP in bone tissue engineering are reviewed to aid the future research and application of BP. Full article
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16 pages, 2362 KiB  
Review
Assembly of Protein Cages for Drug Delivery
by Xiaoxuan Yu, Zihui Weng, Ziyang Zhao, Jiayun Xu, Zhenhui Qi and Junqiu Liu
Pharmaceutics 2022, 14(12), 2609; https://doi.org/10.3390/pharmaceutics14122609 - 26 Nov 2022
Cited by 6 | Viewed by 2402
Abstract
Nanoparticles (NPs) have been widely used as target delivery vehicles for therapeutic goods; however, compared with inorganic and organic nanomaterials, protein nanomaterials have better biocompatibility and can self-assemble into highly ordered cage-like structures, which are more favorable for applications in targeted drug delivery. [...] Read more.
Nanoparticles (NPs) have been widely used as target delivery vehicles for therapeutic goods; however, compared with inorganic and organic nanomaterials, protein nanomaterials have better biocompatibility and can self-assemble into highly ordered cage-like structures, which are more favorable for applications in targeted drug delivery. In this review, we concentrate on the typical protein cage nanoparticles drugs encapsulation processes, such as drug fusion expression, diffusion, electrostatic contact, covalent binding, and protein cage disassembly/recombination. The usage of protein cage nanoparticles in biomedicine is also briefly discussed. These materials can be utilized to transport small molecules, peptides, siRNA, and other medications for anti-tumor, contrast, etc. Full article
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21 pages, 4866 KiB  
Review
Investigation of Trends in the Research on Transferrin Receptor-Mediated Drug Delivery via a Bibliometric and Thematic Analysis
by Tarnjot Kaur, Jyoti Upadhyay, Sudeep Pukale, Ashish Mathur and Mohd Nazam Ansari
Pharmaceutics 2022, 14(12), 2574; https://doi.org/10.3390/pharmaceutics14122574 - 23 Nov 2022
Cited by 4 | Viewed by 1729
Abstract
This study systematically reviews and characterizes the existing literature on transferrin/transferrin receptor-mediated drug delivery. Transferrin is an iron-binding protein. It can be used as a ligand to deliver various proteins, genes, ions, and drugs to the target site via transferrin receptors for therapeutic [...] Read more.
This study systematically reviews and characterizes the existing literature on transferrin/transferrin receptor-mediated drug delivery. Transferrin is an iron-binding protein. It can be used as a ligand to deliver various proteins, genes, ions, and drugs to the target site via transferrin receptors for therapeutic or diagnostic purposes via transferrin receptors. This study is based on a cross-sectional bibliometric analysis of 583 papers limited to the subject areas of pharmacology, toxicology, and pharmaceutics as extracted from the Scopus database in mid-September 2022. The data were analyzed, and we carried out a performance analysis and science mapping. There was a significant increase in research from 2018 onward. The countries that contributed the most were the USA and China, and most of the existing research was found to be from single-country publications. Research studies on transferrin/transferrin receptor-mediated drug delivery focus on drug delivery across the blood–brain barrier in the form of nanoparticles. The thematic analysis revealed four themes: transferrin/transferrin receptor-mediated drug delivery to the brain, cancer cells, gene therapy, nanoparticles, and liposomes as drug delivery systems. This study is relevant to academics, practitioners, and decision makers interested in targeted and site-specific drug delivery. Full article
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23 pages, 3953 KiB  
Review
Surface Modification with Particles Coated or Made of Polymer Multilayers
by Konstantinos T. Kotoulas, Jack Campbell, Andre G. Skirtach, Dmitry Volodkin and Anna Vikulina
Pharmaceutics 2022, 14(11), 2483; https://doi.org/10.3390/pharmaceutics14112483 - 16 Nov 2022
Cited by 4 | Viewed by 1681
Abstract
The coating of particles or decomposable cores with polyelectrolytes via Layer-by-Layer (LbL) assembly creates free-standing LbL-coated functional particles. Due to the numerous functions that their polymers can bestow, the particles are preferentially selected for a plethora of applications, including, but not limited to [...] Read more.
The coating of particles or decomposable cores with polyelectrolytes via Layer-by-Layer (LbL) assembly creates free-standing LbL-coated functional particles. Due to the numerous functions that their polymers can bestow, the particles are preferentially selected for a plethora of applications, including, but not limited to coatings, cargo-carriers, drug delivery vehicles and fabric enhancements. The number of publications discussing the fabrication and usage of LbL-assembled particles has consistently increased over the last vicennial. However, past literature fails to either mention or expand upon how these LbL-assembled particles immobilize on to a solid surface. This review evaluates examples of LbL-assembled particles that have been immobilized on to solid surfaces. To aid in the formulation of a mechanism for immobilization, this review examines which forces and factors influence immobilization, and how the latter can be confirmed. The predominant forces in the immobilization of the particles studied here are the Coulombic, capillary, and adhesive forces; hydrogen bonding as well as van der Waal’s and hydrophobic interactions are also considered. These are heavily dependent on the factors that influenced immobilization, such as the particle morphology and surface charge. The shape of the LbL particle is related to the particle core, whereas the charge was dependant on the outermost polyelectrolyte in the multilayer coating. The polyelectrolytes also determine the type of bonding that a particle can form with a solid surface. These can be via either physical (non-covalent) or chemical (covalent) bonds; the latter enforcing a stronger immobilization. This review proposes a fundamental theory for immobilization pathways and can be used to support future research in the field of surface patterning and for the general modification of solid surfaces with polymer-based nano- and micro-sized polymer structures. Full article
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26 pages, 7754 KiB  
Review
Preparation of Fluorescent Carbon Dots Composites and Their Potential Applications in Biomedicine and Drug Delivery—A Review
by Yaru Chai, Yashan Feng, Kun Zhang and Jingan Li
Pharmaceutics 2022, 14(11), 2482; https://doi.org/10.3390/pharmaceutics14112482 - 16 Nov 2022
Cited by 12 | Viewed by 2913
Abstract
Carbon dots (CDs), a new member of carbon nanostructures, rely on surface modification and functionalization for their good fluorescence phosphorescence and excellent physical and chemical properties, including small size (<10 nm), high chemical stability, biocompatibility, non-toxicity, low cost, and easy synthesis. In the [...] Read more.
Carbon dots (CDs), a new member of carbon nanostructures, rely on surface modification and functionalization for their good fluorescence phosphorescence and excellent physical and chemical properties, including small size (<10 nm), high chemical stability, biocompatibility, non-toxicity, low cost, and easy synthesis. In the field of medical research on cancer (IARC), CDs, a new material with unique optical properties as a photosensitizer, are being applied to heating local apoptosis induction of cancer cells. In addition, imaging tools can also be combined with a drug to form the nanometer complex compound, the imaging guidance for multi-function dosage, so as to improve the efficiency of drug delivery, which also plays a big role in genetic diagnosis. This paper mainly includes three parts: The first part briefly introduces the synthesis and preparation of carbon dots, and summarizes the advantages and disadvantages of different preparation methods; The second part introduces the preparation methods of carbon dot composites. Finally, the application status of carbon dot composites in biomedicine, cancer theranostics, drug delivery, electrochemistry, and photocatalysis is summarized. Full article
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23 pages, 2456 KiB  
Review
Journey of Rosmarinic Acid as Biomedicine to Nano-Biomedicine for Treating Cancer: Current Strategies and Future Perspectives
by Motamarri Venkata Naga Lalitha Chaitanya, Arya Kadukkattil Ramanunny, Malakapogu Ravindra Babu, Monica Gulati, Sukriti Vishwas, Thakur Gurjeet Singh, Dinesh Kumar Chellappan, Jon Adams, Kamal Dua and Sachin Kumar Singh
Pharmaceutics 2022, 14(11), 2401; https://doi.org/10.3390/pharmaceutics14112401 - 07 Nov 2022
Cited by 10 | Viewed by 2388
Abstract
Rosmarinic acid (RA) is a polyphenolic metabolite found in various culinary, dietary sources, and medicinal plants like Coleus scutellarioides (Linn) Benth., Lavandula angustifolia Linn., Mellisa officinalis Linn., Origanum vulgare Linn., Rosmarinus officinalis Linn., Zataria multiflora Boiss. and Zhumeria majdae Rech. F. Apart from [...] Read more.
Rosmarinic acid (RA) is a polyphenolic metabolite found in various culinary, dietary sources, and medicinal plants like Coleus scutellarioides (Linn) Benth., Lavandula angustifolia Linn., Mellisa officinalis Linn., Origanum vulgare Linn., Rosmarinus officinalis Linn., Zataria multiflora Boiss. and Zhumeria majdae Rech. F. Apart from its dietary and therapeutic values, RA is an important anticancer phytochemical owing to its multi-targeting anticancer mechanism. These properties provide a scope for RA’s therapeutic uses beyond its traditional use as a dietary source. However, its oral bioavailability is limited due to its poor solubility and permeability. This impedes its efficacy in treating cancer. Indeed, in recent years, tremendous efforts have been put towards the development of nanoformulations of RA for treating cancer. However, this research is in its initial stage as bringing a nanoparticle into the market itself is associated with many issues such as stability, toxicity, and scale-up issues. Considering these pitfalls during formulation development and overcoming them would surely provide a new face to RA as a nanomedicine to treat cancer. A literature search was conducted to systematically review the various biological sources, extraction techniques, and anticancer mechanisms through which RA showed multiple therapeutic effects. Various nanocarriers of RA pertaining to its anticancer activity are also discussed in this review. Full article
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21 pages, 2015 KiB  
Review
Advances of Cobalt Nanomaterials as Anti-Infection Agents, Drug Carriers, and Immunomodulators for Potential Infectious Disease Treatment
by Yuhe Ma, Wensen Lin, Yongdui Ruan, Hongmei Lu, Shuhao Fan, Dongsheng Chen, Yuhe Huang, Tangxin Zhang, Jiang Pi and Jun-Fa Xu
Pharmaceutics 2022, 14(11), 2351; https://doi.org/10.3390/pharmaceutics14112351 - 31 Oct 2022
Cited by 5 | Viewed by 1758
Abstract
Infectious diseases remain the most serious public health issue, which requires the development of more effective strategies for infectious control. As a kind of ultra-trace element, cobalt is essential to the metabolism of different organisms. In recent decades, nanotechnology has attracted increasing attention [...] Read more.
Infectious diseases remain the most serious public health issue, which requires the development of more effective strategies for infectious control. As a kind of ultra-trace element, cobalt is essential to the metabolism of different organisms. In recent decades, nanotechnology has attracted increasing attention worldwide due to its wide application in different areas, including medicine. Based on the important biological roles of cobalt, cobalt nanomaterials have recently been widely developed for their attractive biomedical applications. With advantages such as low costs in preparation, hypotoxicity, photothermal conversion abilities, and high drug loading ability, cobalt nanomaterials have been proven to show promising potential in anticancer and anti-infection treatment. In this review, we summarize the characters of cobalt nanomaterials, followed by the advances in their biological functions and mechanisms. More importantly, we emphatically discuss the potential of cobalt nanomaterials as anti-infectious agents, drug carriers, and immunomodulators for anti-infection treatments, which might be helpful to facilitate progress in future research of anti-infection therapy. Full article
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20 pages, 8780 KiB  
Review
Application of DFT Calculations in Designing Polymer-Based Drug Delivery Systems: An Overview
by Oluwasegun Chijioke Adekoya, Gbolahan Joseph Adekoya, Emmanuel Rotimi Sadiku, Yskandar Hamam and Suprakas Sinha Ray
Pharmaceutics 2022, 14(9), 1972; https://doi.org/10.3390/pharmaceutics14091972 - 19 Sep 2022
Cited by 14 | Viewed by 6299
Abstract
Drug delivery systems transfer medications to target locations throughout the body. These systems are often made up of biodegradable and bioabsorbable polymers acting as delivery components. The introduction of density functional theory (DFT) has tremendously aided the application of computational material science in [...] Read more.
Drug delivery systems transfer medications to target locations throughout the body. These systems are often made up of biodegradable and bioabsorbable polymers acting as delivery components. The introduction of density functional theory (DFT) has tremendously aided the application of computational material science in the design and development of drug delivery materials. The use of DFT and other computational approaches avoids time-consuming empirical processes. Therefore, this review explored how the DFT computation may be utilized to explain some of the features of polymer-based drug delivery systems. First, we went through the key aspects of DFT and provided some context. Then we looked at the essential characteristics of a polymer-based drug delivery system that DFT simulations could predict. We observed that the Gaussian software had been extensively employed by researchers, particularly with the B3LYP functional and 6-31G(d, p) basic sets for polymer-based drug delivery systems. However, to give researchers a choice of basis set for modelling complicated organic systems, such as polymer–drug complexes, we then offered possible resources and presented the future trend. Full article
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18 pages, 1291 KiB  
Review
The Development and Clinical Applications of Oral Arsenic Trioxide for Acute Promyelocytic Leukaemia and Other Diseases
by Lynn Chin, Cyrus R. Kumana, Yok-Lam Kwong and Harinder Gill
Pharmaceutics 2022, 14(9), 1945; https://doi.org/10.3390/pharmaceutics14091945 - 14 Sep 2022
Cited by 5 | Viewed by 2198
Abstract
Appreciation of the properties of arsenic trioxide (ATO) has redefined the treatment landscape for acute promyelocytic leukaemia (APL) and offers promise as a treatment for numerous other diseases. The benefits of ATO in patients with APL is related to its ability to counteract [...] Read more.
Appreciation of the properties of arsenic trioxide (ATO) has redefined the treatment landscape for acute promyelocytic leukaemia (APL) and offers promise as a treatment for numerous other diseases. The benefits of ATO in patients with APL is related to its ability to counteract the effects of PML::RARA, an oncoprotein that is invariably detected in the blood or bone marrow of affected individuals. The PML::RARA oncoprotein is degraded specifically by binding to ATO. Thus ATO, in combination with all-trans retinoic acid, has become the curative treatment for ATO. The multiple mechanisms of action of ATO has also paved the way for application in various condition encompassing autoimmune or inflammatory disorders, solid organ tumours, lymphomas and other subtypes of AML. The development of oral formulation of ATO (oral ATO) has reduced costs of treatment and improved treatment convenience allowing widespread applicability. In this review, we discuss the mechanisms of action of ATO, the development of oral ATO, and the applications of oral ATO in APL and other diseases. Full article
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23 pages, 2682 KiB  
Review
Nanotechnology-Based Combinatorial Anti-Glioblastoma Therapies: Moving from Terminal to Treatable
by Amir Barzegar Behrooz, Zahra Talaie and Amir Syahir
Pharmaceutics 2022, 14(8), 1697; https://doi.org/10.3390/pharmaceutics14081697 - 15 Aug 2022
Cited by 7 | Viewed by 2864
Abstract
Aggressive glioblastoma (GBM) has no known treatment as a primary brain tumor. Since the cancer is so heterogeneous, an immunosuppressive tumor microenvironment (TME) exists, and the blood–brain barrier (BBB) prevents chemotherapeutic chemicals from reaching the central nervous system (CNS), therapeutic success for GBM [...] Read more.
Aggressive glioblastoma (GBM) has no known treatment as a primary brain tumor. Since the cancer is so heterogeneous, an immunosuppressive tumor microenvironment (TME) exists, and the blood–brain barrier (BBB) prevents chemotherapeutic chemicals from reaching the central nervous system (CNS), therapeutic success for GBM has been restricted. Drug delivery based on nanocarriers and nanotechnology has the potential to be a handy tool in the continuing effort to combat the challenges of treating GBM. There are various new therapies being tested to extend survival time. Maximizing therapeutic effectiveness necessitates using many treatment modalities at once. In the fight against GBM, combination treatments outperform individual ones. Combination therapies may be enhanced by using nanotechnology-based delivery techniques. Nano-chemotherapy, nano-chemotherapy–radiation, nano-chemotherapy–phototherapy, and nano-chemotherapy–immunotherapy for GBM are the focus of the current review to shed light on the current status of innovative designs. Full article
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22 pages, 2367 KiB  
Review
Supercritical Fluid Technologies for the Incorporation of Synthetic and Natural Active Compounds into Materials for Drug Formulation and Delivery
by Katja Andrina Kravanja, Matjaž Finšgar, Željko Knez and Maša Knez Marevci
Pharmaceutics 2022, 14(8), 1670; https://doi.org/10.3390/pharmaceutics14081670 - 11 Aug 2022
Cited by 12 | Viewed by 2350
Abstract
Various active compounds isolated from natural sources exhibit remarkable benefits, making them attractive for pharmaceutical and biomedical applications, such as antioxidant, antimicrobial, and anti-inflammatory activities, which contribute to the treatment of cardiovascular diseases, neurodegenerative disorders, various types of cancer, diabetes, and obesity. However, [...] Read more.
Various active compounds isolated from natural sources exhibit remarkable benefits, making them attractive for pharmaceutical and biomedical applications, such as antioxidant, antimicrobial, and anti-inflammatory activities, which contribute to the treatment of cardiovascular diseases, neurodegenerative disorders, various types of cancer, diabetes, and obesity. However, their major drawbacks are their reactivity, instability, relatively poor water solubility, and consequently low bioavailability. Synthetic drugs often face similar challenges associated with inadequate solubility or burst release in gastrointestinal media, despite being otherwise a safe and effective option for the treatment of numerous diseases. Therefore, drug-eluting pharmaceutical formulations have been of great importance over the years in efforts to improve the bioavailability of active compounds by increasing their solubility and achieving their controlled release in body media. This review highlights the success of the fabrication of micro- and nanoformulations using environmentally friendly supercritical fluid technologies for the processing and incorporation of active compounds. Several novel approaches, namely micronization to produce micro- and nano-sized particles, supercritical drying to produce aerogels, supercritical foaming, and supercritical solvent impregnation, are described in detail, along with the currently available drug delivery data for these formulations. Full article
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16 pages, 2367 KiB  
Review
The Current State of the Art in PARP Inhibitor-Based Delivery Nanosystems
by Lisha Cai, Xiaoling Xu and Wei Chen
Pharmaceutics 2022, 14(8), 1647; https://doi.org/10.3390/pharmaceutics14081647 - 08 Aug 2022
Cited by 4 | Viewed by 2045
Abstract
Poly (adenosine diphosphate [ADP]–ribose) polymerases inhibitors (PARPi), the first clinically approved drug that exhibits synthetic lethality, are moving to the forefront of cancer treatments. Currently, the oral bioavailability of PARPi is quite low; thus, it is a major challenge to effectively and safely [...] Read more.
Poly (adenosine diphosphate [ADP]–ribose) polymerases inhibitors (PARPi), the first clinically approved drug that exhibits synthetic lethality, are moving to the forefront of cancer treatments. Currently, the oral bioavailability of PARPi is quite low; thus, it is a major challenge to effectively and safely deliver PARPi during clinical cancer therapy. Nanotechnology has greatly advanced the development of drug delivery. Based on the basic characteristics and various forms of nanoparticles, drug delivery systems can prolong the time that drugs circulate, realize the controlled release of drugs, provide drugs with an active targeting ability, and spatiotemporally present combination treatment. Furthermore, nanosystems may not only enhance drug efficiency but also reduce adverse side effects. This review focuses on strategies involving nanoparticle-based delivery for PARPi, including single administration and codelivery with other agents. We believe that nanosystems have great potential in advancing PARPi efficacy for cancer therapy. Full article
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32 pages, 2953 KiB  
Review
When Natural Compounds Meet Nanotechnology: Nature-Inspired Nanomedicines for Cancer Immunotherapy
by Linna Yu, Yi Jin, Mingjie Song, Yu Zhao and Huaqing Zhang
Pharmaceutics 2022, 14(8), 1589; https://doi.org/10.3390/pharmaceutics14081589 - 30 Jul 2022
Cited by 10 | Viewed by 2711
Abstract
Recent significant strides of natural compounds in immunomodulation have highlighted their great potential against cancer. Despite many attempts being made for cancer immunotherapy, the biomedical application of natural compounds encounters a bottleneck because of their unclear mechanisms, low solubility and bioavailability, and limited [...] Read more.
Recent significant strides of natural compounds in immunomodulation have highlighted their great potential against cancer. Despite many attempts being made for cancer immunotherapy, the biomedical application of natural compounds encounters a bottleneck because of their unclear mechanisms, low solubility and bioavailability, and limited efficacy. Herein, we summarize the immune regulatory mechanisms of different natural compounds at each step of the cancer-immunity cycle and highlight their anti-tumor potential and current limitations. We then propose and present various drug delivery strategies based on nanotechnology, including traditional nanoparticles (NPs)-based delivery strategies (lipid-based NPs, micelles, and polysaccharide/peptide/protein-based NPs) and novel delivery strategies (cell-derived NPs and carrier-free NPs), thus providing solutions to break through existing bottlenecks. Furthermore, representative applications of nature-inspired nanomedicines are also emphasized in detail with the advantages and disadvantages discussed. Finally, the challenges and prospects of natural compounds for cancer immunotherapy are provided, hopefully, to facilitate their far-reaching development toward clinical translation. Full article
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28 pages, 1652 KiB  
Review
A Comprehensive Review of the Evolution of Insulin Development and Its Delivery Method
by Vaisnevee Sugumar, Kuan Ping Ang, Ahmed F. Alshanon, Gautam Sethi, Phelim Voon Chen Yong, Chung Yeng Looi and Won Fen Wong
Pharmaceutics 2022, 14(7), 1406; https://doi.org/10.3390/pharmaceutics14071406 - 04 Jul 2022
Cited by 9 | Viewed by 3692
Abstract
The year 2021 marks the 100th anniversary of the momentous discovery of insulin. Through years of research and discovery, insulin has evolved from poorly defined crude extracts of animal pancreas to recombinant human insulin and analogues that can be prescribed and administered with [...] Read more.
The year 2021 marks the 100th anniversary of the momentous discovery of insulin. Through years of research and discovery, insulin has evolved from poorly defined crude extracts of animal pancreas to recombinant human insulin and analogues that can be prescribed and administered with high accuracy and efficacy. However, there are still many challenges ahead in clinical settings, particularly with respect to maintaining optimal glycemic control whilst minimizing the treatment-related side effects of hypoglycemia and weight gain. In this review, the chronology of the development of rapid-acting, short-acting, intermediate-acting, and long-acting insulin analogues, as well as mixtures and concentrated formulations that offer the potential to meet this challenge, are summarized. In addition, we also summarize the latest advancements in insulin delivery methods, along with advancement to clinical trials. This review provides insights on the development of insulin treatment for diabetes mellitus that may be useful for clinicians in meeting the needs of their individual patients. However, it is important to note that as of now, none of the new technologies mentioned have superseded the existing method of subcutaneous administration of insulin. Full article
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26 pages, 3927 KiB  
Review
Nitric Oxide-Releasing Platforms for Treating Cardiovascular Disease
by Mingyue He, Deping Wang, Yumei Xu, Fangying Jiang, Jian Zheng, Yanlin Feng, Jimin Cao and Xin Zhou
Pharmaceutics 2022, 14(7), 1345; https://doi.org/10.3390/pharmaceutics14071345 - 25 Jun 2022
Cited by 8 | Viewed by 2761
Abstract
Cardiovascular disease (CVD) is the first leading cause of death globally. Nitric oxide (NO) is an important signaling molecule that mediates diverse processes in the cardiovascular system, thereby providing a fundamental basis for NO-based therapy of CVD. At present, numerous prodrugs have been [...] Read more.
Cardiovascular disease (CVD) is the first leading cause of death globally. Nitric oxide (NO) is an important signaling molecule that mediates diverse processes in the cardiovascular system, thereby providing a fundamental basis for NO-based therapy of CVD. At present, numerous prodrugs have been developed to release NO in vivo. However, the clinical application of these prodrugs still faces many problems, including the low payloads, burst release, and non-controlled delivery. To address these, various biomaterial-based platforms have been developed as the carriers to deliver NO to the targeted tissues in a controlled and sustained manner. This review aims to summarize recent developments of various therapeutic platforms, engineered to release NO for the treatment of CVD. In addition, two potential strategies to improve the effectiveness of existing NO therapy are also discussed, including the combination of NO-releasing platforms and either hydrogen sulfide-based therapy or stem cell therapy. Hopefully, some NO-releasing platforms may provide important therapeutic benefits for CVD. Full article
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19 pages, 1059 KiB  
Review
Bispecific Antibodies in Cancer Immunotherapy: A Novel Response to an Old Question
by Camila Ordóñez-Reyes, Juan Esteban Garcia-Robledo, Diego F. Chamorro, Andrés Mosquera, Liliana Sussmann, Alejandro Ruiz-Patiño, Oscar Arrieta, Lucia Zatarain-Barrón, Leonardo Rojas, Alessandro Russo, Diego de Miguel-Perez, Christian Rolfo and Andrés F. Cardona
Pharmaceutics 2022, 14(6), 1243; https://doi.org/10.3390/pharmaceutics14061243 - 11 Jun 2022
Cited by 13 | Viewed by 6164
Abstract
Immunotherapy has redefined the treatment of cancer patients and it is constantly generating new advances and approaches. Among the multiple options of immunotherapy, bispecific antibodies (bsAbs) represent a novel thoughtful approach. These drugs integrate the action of the immune system in a strategy [...] Read more.
Immunotherapy has redefined the treatment of cancer patients and it is constantly generating new advances and approaches. Among the multiple options of immunotherapy, bispecific antibodies (bsAbs) represent a novel thoughtful approach. These drugs integrate the action of the immune system in a strategy to redirect the activation of innate and adaptive immunity toward specific antigens and specific tumor locations. Here we discussed some basic aspects of the design and function of bsAbs, their main challenges and the state-of-the-art of these molecules in the treatment of hematological and solid malignancies and future perspectives. Full article
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18 pages, 1565 KiB  
Review
Plant-Derived Exosomes as a Drug-Delivery Approach for the Treatment of Inflammatory Bowel Disease and Colitis-Associated Cancer
by Ying Cai, Luoxin Zhang, Youjian Zhang and Rong Lu
Pharmaceutics 2022, 14(4), 822; https://doi.org/10.3390/pharmaceutics14040822 - 08 Apr 2022
Cited by 32 | Viewed by 4962
Abstract
Inflammatory bowel disease (IBD) is a chronic recurrent intestinal disease and includes Crohn’s disease (CD) and ulcerative colitis (UC). Due to the complex etiology of colitis, the current treatments of IBD are quite limited and are mainly concentrated on the remission of the [...] Read more.
Inflammatory bowel disease (IBD) is a chronic recurrent intestinal disease and includes Crohn’s disease (CD) and ulcerative colitis (UC). Due to the complex etiology of colitis, the current treatments of IBD are quite limited and are mainly concentrated on the remission of the disease. In addition, the side effects of conventional drugs on the body cannot be ignored. IBD also has a certain relationship with colitis-associated cancer (CAC), and inflammatory cells can produce a large number of tumor-promoting cytokines to promote tumor progression. In recent years, exosomes from plants have been found to have the ability to load drugs to target the intestine and have great potential for the treatment of intestinal diseases. This plant-derived exosome-targeting delivery system can load chemical or nucleic acid drugs and deliver them to intestinal inflammatory sites stably and efficiently. This review summarizes the pathophysiological characteristics of IBD and CAC as well as the application and prospect of plant exosomes in the treatment of IBD and CAC. Full article
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29 pages, 3036 KiB  
Review
Bee-Derived Products: Chemical Composition and Applications in Skin Tissue Engineering
by Corina Dana Dumitru, Ionela Andreea Neacsu, Alexandru Mihai Grumezescu and Ecaterina Andronescu
Pharmaceutics 2022, 14(4), 750; https://doi.org/10.3390/pharmaceutics14040750 - 30 Mar 2022
Cited by 18 | Viewed by 3996
Abstract
Skin tissue regeneration is one of the population’s most common problems, and the complications that may appear in the healing process can have detrimental consequences. An alternative to conventional treatments could be represented by sustainable materials based on natural products, such as honey [...] Read more.
Skin tissue regeneration is one of the population’s most common problems, and the complications that may appear in the healing process can have detrimental consequences. An alternative to conventional treatments could be represented by sustainable materials based on natural products, such as honey and its derivates (propolis, royal jelly, bee pollen, beeswax, and bee venom). They exhibit significant inhibitory activities against bacteria and have great potential in dermal tissue regeneration. Research in the pharmaceutical field demonstrates that conventional medication combined with bee products can deliver better results. The advantages include minimizing side effects and maintaining the same effectiveness by using low concentrations of antibiotic, anti-inflammatory, or chemotherapy drugs. Several studies suggested that bee products can replace the antimicrobial activity and efficiency of antibiotics, but further investigation is needed to establish a topical mixture’s potential, including honey, royal jelly, and propolis. Bee products seem to complete each other’s deficiencies, and their mixture may have a better impact on the wound healing process. The topic addressed in this paper highlights the usefulness of honey, propolis, royal jelly, bee pollen, beeswax, and bee venom in the re-epithelization process and against most common bacterial infections. Full article
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33 pages, 20278 KiB  
Review
Conventional and Recent Trends of Scaffolds Fabrication: A Superior Mode for Tissue Engineering
by Islam M. Adel, Mohamed F. ElMeligy and Nermeen A. Elkasabgy
Pharmaceutics 2022, 14(2), 306; https://doi.org/10.3390/pharmaceutics14020306 - 27 Jan 2022
Cited by 36 | Viewed by 4517
Abstract
Tissue regeneration is an auto-healing mechanism, initiating immediately following tissue damage to restore normal tissue structure and function. This falls in line with survival instinct being the most dominant instinct for any living organism. Nevertheless, the process is slow and not feasible in [...] Read more.
Tissue regeneration is an auto-healing mechanism, initiating immediately following tissue damage to restore normal tissue structure and function. This falls in line with survival instinct being the most dominant instinct for any living organism. Nevertheless, the process is slow and not feasible in all tissues, which led to the emergence of tissue engineering (TE). TE aims at replacing damaged tissues with new ones. To do so, either new tissue is being cultured in vitro and then implanted, or stimulants are implanted into the target site to enhance endogenous tissue formation. Whichever approach is used, a matrix is used to support tissue growth, known as ‘scaffold’. In this review, an overall look at scaffolds fabrication is discussed, starting with design considerations and different biomaterials used. Following, highlights of conventional and advanced fabrication techniques are attentively presented. The future of scaffolds in TE is ever promising, with the likes of nanotechnology being investigated for scaffold integration. The constant evolvement of organoids and biofluidics with the eventual inclusion of organ-on-a-chip in TE has shown a promising prospect of what the technology might lead to. Perhaps the closest technology to market is 4D scaffolds following the successful implementation of 4D printing in other fields. Full article
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