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Open AccessArticle

Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous

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Pharmaceutics 2023, 15(4), 1264; https://doi.org/10.3390/pharmaceutics15041264 - 18 Apr 2023

Cited by 1 | Viewed by 786

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

A New Strategy for Nucleic Acid Delivery and Protein Expression Using Biocompatible Nanohydrogels of Predefined Sizes

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Pharmaceutics 2023, 15(3), 961; https://doi.org/10.3390/pharmaceutics15030961 - 16 Mar 2023

Viewed by 830

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Dexamethasone and Dexamethasone Phosphate: Effect on DMPC Membrane Models

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Candelaria Ines Cámara

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Matías Ariel Crosio

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Ana Valeria Juarez

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Natalia Wilke

Pharmaceutics 2023, 15(3), 844; https://doi.org/10.3390/pharmaceutics15030844 - 04 Mar 2023

Viewed by 959

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Hydrophilic High Drug-Loaded 3D Printed Gastroretentive System with Robust Release Kinetics

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Gloria Mora-Castaño

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Mónica Millán-Jiménez

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Isidoro Caraballo

Pharmaceutics 2023, 15(3), 842; https://doi.org/10.3390/pharmaceutics15030842 - 04 Mar 2023

Cited by 2 | Viewed by 978

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Composite PLGA–Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration

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Georgia K. Pouroutzidou

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Lambrini Papadopoulou

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Maria Lazaridou

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Konstantinos Tsachouridis

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Chrysanthi Papoulia

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Dimitra Patsiaoura

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Ioannis Tsamesidis

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Konstantinos Chrissafis

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George Vourlias

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Konstantinos M. Paraskevopoulos

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Antonios D. Anastasiou

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Dimitrios N. Bikiaris

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Eleana Kontonasaki

Pharmaceutics 2023, 15(3), 819; https://doi.org/10.3390/pharmaceutics15030819 - 02 Mar 2023

Cited by 3 | Viewed by 1301

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

3D-Printing of Silk Nanofibrils Reinforced Alginate for Soft Tissue Engineering

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Zahra Mohammadpour

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Mahshid Kharaziha

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Ali Zarrabi

Pharmaceutics 2023, 15(3), 763; https://doi.org/10.3390/pharmaceutics15030763 - 24 Feb 2023

Cited by 5 | Viewed by 1169

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

HER2-Specific Peptide (LTVSPWY) and Antibody (Herceptin) Targeted Core Cross-Linked Micelles for Breast Cancer: A Comparative Study

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Nazende Nur Bayram

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Gizem Tuğçe Ulu

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Nusaibah Abdulsalam Abdulhadi

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Pharmaceutics 2023, 15(3), 733; https://doi.org/10.3390/pharmaceutics15030733 - 22 Feb 2023

Viewed by 1303

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessFeature PaperArticle

Synthesis of Magnetic Iron Oxide-Incorporated Cellulose Composite Particles: An Investigation on Antioxidant Properties and Drug Delivery Applications

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Muhammad Sarwar Hossain

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Hasi Rani Barai

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Md. Rezaul Haque

Pharmaceutics 2023, 15(3), 732; https://doi.org/10.3390/pharmaceutics15030732 - 22 Feb 2023

Cited by 1 | Viewed by 1210

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Intracellular Delivery of Itaconate by Metal–Organic Framework-Anchored Hydrogel Microspheres for Osteoarthritis Therapy

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Pharmaceutics 2023, 15(3), 724; https://doi.org/10.3390/pharmaceutics15030724 - 22 Feb 2023

Cited by 1 | Viewed by 1121

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

The Ability of Some Polysaccharides to Disaggregate Lysozyme Amyloid Fibrils and Renature the Protein

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Olga Makshakova

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Liliya Bogdanova

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Dzhigangir Faizullin

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Diliara Khaibrakhmanova

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Pharmaceutics 2023, 15(2), 624; https://doi.org/10.3390/pharmaceutics15020624 - 13 Feb 2023

Cited by 1 | Viewed by 1094

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Intranasal Delivery of a Silymarin Loaded Microemulsion for the Effective Treatment of Parkinson’s Disease in Rats: Formulation, Optimization, Characterization, and In Vivo Evaluation

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Mohammed Kanan Alshammari

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Mohammed Omar Alzahrani

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Faisal Khaled Almaysari

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Abdulrahman Omar Alzahrani

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Ahmed Faraj Elkerdasy

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Sachin Kumar Singh

Pharmaceutics 2023, 15(2), 618; https://doi.org/10.3390/pharmaceutics15020618 - 12 Feb 2023

Viewed by 1469

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Development of Autopolymerizing Resin Material with Antimicrobial Properties Using Montmorillonite and Nanoporous Silica

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Pharmaceutics 2023, 15(2), 544; https://doi.org/10.3390/pharmaceutics15020544 - 06 Feb 2023

Viewed by 917

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Rapidly Dissolving Microneedles for the Delivery of Steroid-Loaded Nanoparticles Intended for the Treatment of Inflammatory Skin Diseases

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Hala Dawud

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Aiman Abu Ammar

Pharmaceutics 2023, 15(2), 526; https://doi.org/10.3390/pharmaceutics15020526 - 04 Feb 2023

Cited by 6 | Viewed by 2223

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Honokiol-Loaded Nanoemulsion for Glioblastoma Treatment: Statistical Optimization, Physicochemical Characterization, and an In Vitro Toxicity Assay

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Aleksandra Majchrzak-Celińska

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Violetta Krajka-Kuźniak

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Maciej Stawny

Pharmaceutics 2023, 15(2), 448; https://doi.org/10.3390/pharmaceutics15020448 - 29 Jan 2023

Cited by 3 | Viewed by 1074

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Poly(Glycerol) Microparticles as Drug Delivery Vehicle for Biomedical Use

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Pharmaceutics 2023, 15(2), 384; https://doi.org/10.3390/pharmaceutics15020384 - 23 Jan 2023

Cited by 1 | Viewed by 1392

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Interactions between DMPC Model Membranes, the Drug Naproxen, and the Saponin β-Aescin

by

Pia Hägerbäumer

,

Friederike Gräbitz-Bräuer

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and

Pharmaceutics 2023, 15(2), 379; https://doi.org/10.3390/pharmaceutics15020379 - 22 Jan 2023

Viewed by 1255

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

T_{m}

. The incorporation of naproxen and aescin distorted the lipid membrane structure and lowers

T_{m}

. Below

T_{m}

, 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

T_{m}

, 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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

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 1 | Viewed by 1155

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Nano-Spray-Dried Levocetirizine Dihydrochloride with Mucoadhesive Carriers and Cyclodextrins for Nasal Administration

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Pharmaceutics 2023, 15(2), 317; https://doi.org/10.3390/pharmaceutics15020317 - 18 Jan 2023

Cited by 2 | Viewed by 1274

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

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 1 | Viewed by 884

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

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

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and

Pharmaceutics 2023, 15(1), 301; https://doi.org/10.3390/pharmaceutics15010301 - 16 Jan 2023

Cited by 1 | Viewed by 1715

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

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

Viewed by 1017

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Effect of Organomontmorillonite-Cloisite^® 20A Incorporation on the Structural and Drug Release Properties of Ureasil–PEO Hybrid

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Pharmaceutics 2023, 15(1), 33; https://doi.org/10.3390/pharmaceutics15010033 - 22 Dec 2022

Cited by 1 | Viewed by 857

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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3D Printed Osteoblast–Alginate/Collagen Hydrogels Promote Survival, Proliferation and Mineralization at Low Doses of Strontium Calcium Polyphosphate

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Pharmaceutics 2023, 15(1), 11; https://doi.org/10.3390/pharmaceutics15010011 - 20 Dec 2022

Cited by 1 | Viewed by 1512

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

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,

,

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,

,

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 3 | Viewed by 1239

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Influence of the Alcohols on the ZnO Synthesis and Its Properties: The Photocatalytic and Antimicrobial Activities

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Ovidiu-Cristian Oprea

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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 15 | Viewed by 2161

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Artificial Base-Directed In Vivo Formulation of Aptamer–Drug Conjugates with Albumin for Long Circulation and Targeted Delivery

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Pharmaceutics 2022, 14(12), 2781; https://doi.org/10.3390/pharmaceutics14122781 - 13 Dec 2022

Cited by 1 | Viewed by 1290

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Mesoporous Silica Promotes Osteogenesis of Human Adipose-Derived Stem Cells Identified by a High-Throughput Microfluidic Chip Assay

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Pharmaceutics 2022, 14(12), 2730; https://doi.org/10.3390/pharmaceutics14122730 - 06 Dec 2022

Cited by 1 | Viewed by 1103

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Superparamagnetic Iron Oxide Nanoparticles and Curcumin Equally Promote Neuronal Branching Morphogenesis in the Absence of Nerve Growth Factor in PC12 Cells

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Pharmaceutics 2022, 14(12), 2692; https://doi.org/10.3390/pharmaceutics14122692 - 01 Dec 2022

Cited by 1 | Viewed by 962

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Hybrid Polydimethylsiloxane (PDMS) Incorporated Thermogelling System for Effective Liver Cancer Treatment

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Pharmaceutics 2022, 14(12), 2623; https://doi.org/10.3390/pharmaceutics14122623 - 28 Nov 2022

Viewed by 1168

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Quality by Design Based Formulation of Xanthohumol Loaded Solid Lipid Nanoparticles with Improved Bioavailability and Anticancer Effect against PC-3 Cells

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Malakapogu Ravindra Babu

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Rajesh Kumar

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Monica Gulati

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Kuppusamy Gowthamarajan

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SubbaRao V. Madhunapantula

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Dinesh Kumar Chellappan

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Pharmaceutics 2022, 14(11), 2403; https://doi.org/10.3390/pharmaceutics14112403 - 07 Nov 2022

Cited by 4 | Viewed by 1772

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 C_max (1.07-folds), AUC_0-t (4.70-folds), t_1/2 (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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Development of Guar Gum-Pectin-Based Colon Targeted Solid Self-Nanoemulsifying Drug Delivery System of Xanthohumol

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Pharmaceutics 2022, 14(11), 2384; https://doi.org/10.3390/pharmaceutics14112384 - 05 Nov 2022

Cited by 4 | Viewed by 1427

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

The Role of Hidden Conformers in Determination of Conformational Preferences of Mefenamic Acid by NOESY Spectroscopy

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Konstantin V. Belov

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Luís A. E. Batista de Carvalho

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Alexey A. Dyshin

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Sergey V. Efimov

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Ilya A. Khodov

Pharmaceutics 2022, 14(11), 2276; https://doi.org/10.3390/pharmaceutics14112276 - 24 Oct 2022

Cited by 9 | Viewed by 15396

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

How to Improve Solubility and Dissolution of Irbesartan by Fabricating Ternary Solid Dispersions: Optimization and In-Vitro Characterization

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Pharmaceutics 2022, 14(11), 2264; https://doi.org/10.3390/pharmaceutics14112264 - 23 Oct 2022

Cited by 5 | Viewed by 1731

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Impact of PEGylated Liposomal Doxorubicin and Carboplatin Combination on Glioblastoma

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Hasan Ebrahimi Shahmabadi

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Seyed Ebrahim Alavi

Pharmaceutics 2022, 14(10), 2183; https://doi.org/10.3390/pharmaceutics14102183 - 13 Oct 2022

Cited by 14 | Viewed by 1513

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Pulsed Laser Photo-Crosslinking of Gelatin Methacryloyl Hydrogels for the Controlled Delivery of Chlorpromazine to Combat Antimicrobial Resistance

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Tatiana Tozar

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Simona Nistorescu

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Mihai Boni

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Gratiela Gradisteanu Pircalabioru

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Irina Negut

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Angela Staicu

Pharmaceutics 2022, 14(10), 2121; https://doi.org/10.3390/pharmaceutics14102121 - 06 Oct 2022

Cited by 3 | Viewed by 1361

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Elastin-like Polypeptide Hydrogels for Tunable, Sustained Local Chemotherapy in Malignant Glioma

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Pharmaceutics 2022, 14(10), 2072; https://doi.org/10.3390/pharmaceutics14102072 - 28 Sep 2022

Cited by 4 | Viewed by 1291

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Penicillin and Oxacillin Loaded on PEGylated-Graphene Oxide to Enhance the Activity of the Antibiotics against Methicillin-Resistant Staphylococcus aureus

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Mohadeseh Mohammadi Tabar

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Pharmaceutics 2022, 14(10), 2049; https://doi.org/10.3390/pharmaceutics14102049 - 26 Sep 2022

Cited by 1 | Viewed by 1134

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Co-Delivery of Dihydroartemisinin and Indocyanine Green by Metal-Organic Framework-Based Vehicles for Combination Treatment of Hepatic Carcinoma

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Pharmaceutics 2022, 14(10), 2047; https://doi.org/10.3390/pharmaceutics14102047 - 26 Sep 2022

Cited by 2 | Viewed by 1461

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

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

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Pharmaceutics 2022, 14(10), 2046; https://doi.org/10.3390/pharmaceutics14102046 - 26 Sep 2022

Viewed by 1235

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Fabrication, In Vitro, and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing

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Pharmaceutics 2022, 14(9), 1971; https://doi.org/10.3390/pharmaceutics14091971 - 19 Sep 2022

Cited by 8 | Viewed by 1522

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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Open AccessArticle

Biodegradation of HA and β-TCP Ceramics Regulated by T-Cells

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Pharmaceutics 2022, 14(9), 1962; https://doi.org/10.3390/pharmaceutics14091962 - 16 Sep 2022

Cited by 1 | Viewed by 1230

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

(This article belongs to the Special Issue Sustainable Materials and Technologies for Drug Delivery and Tissue Engineering)

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