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Pharmaceutics
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Smart Drug Delivery Strategies Based on Porous Materials
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Smart Drug Delivery Strategies Based on Porous Materials

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

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 17930

Special Issue Editor

Dr. Aun Raza

E-Mail Website
Guest Editor
School of Pharmacy, The University of Queensland, Woolloongabba 4102, Australia
Interests: oral drug delivery; nanoparticles; silicon and polymeric; antioxidant; anti-inflammatory; antibacterial and anticancer; extraction; metal chelating
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nanocarrier technology is a promising tool for addressing many of the challenges (i.e., low solubility and permeability, instability in the gut and thermolabile, etc.) associated with different drugs for their delivery via different routes, such as oral, nasal, topical, parenteral, etc. Nanoparticles (NPs) are small (10–1000 nm) and, when combined with these therapeutic entities, are responsible for giving new properties, such as a high surface, volume area and better bioavailability. Regarding these nanocarriers, solid nanoparticles, such as porous silica and silicon, are known as promising candidates that can overcome the above problems and produce effects in a controllable and sustainable manner. Porous silica and silicon nanoparticles are widely used as a delivery agent because they possess favourable chemical properties, thermal stability, and biocompatibility. Their unique porous structure facilitates effective loading of drugs and their subsequent controlled release of the target site. Hereby, we invite all researchers to contribute to this Special Issue, which will collect both research and review articles devoted to various aspects of solid nanoparticles in drug delivery.

Dr. Aun Raza
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • silica nanoparticles
  • silicon nanoparticles
  • poorly soluble and permeable drugs
  • thermo- and gastric-labile drugs
  • nanomedicine
  • drug delivery

Published Papers (8 papers)

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Research

14 pages, 4923 KiB  
Article
Intracellular Delivery of Therapeutic Protein via Ultrathin Layered Double Hydroxide Nanosheets
by He Zhang, Anle Ge, Yulin Wang, Boran Xia, Xichu Wang, Zhonghui Zheng, Changsheng Wei, Bo Ma, Lin Zhu, Rose Amal, Sung Lai Jimmy Yun and Zi Gu
Pharmaceutics 2024, 16(3), 422; https://doi.org/10.3390/pharmaceutics16030422 - 19 Mar 2024
Viewed by 784
Abstract
The therapeutic application of biofunctional proteins relies on their intracellular delivery, which is hindered by poor cellular uptake and transport from endosomes to cytoplasm. Herein, we constructed a two-dimensional (2D) ultrathin layered double hydroxide (LDH) nanosheet for the intracellular delivery of a cell-impermeable [...] Read more.
The therapeutic application of biofunctional proteins relies on their intracellular delivery, which is hindered by poor cellular uptake and transport from endosomes to cytoplasm. Herein, we constructed a two-dimensional (2D) ultrathin layered double hydroxide (LDH) nanosheet for the intracellular delivery of a cell-impermeable protein, gelonin, towards efficient and specific cancer treatment. The LDH nanosheet was synthesized via a facile method without using exfoliation agents and showed a high loading capacity of proteins (up to 182%). Using 2D and 3D 4T1 breast cancer cell models, LDH–gelonin demonstrated significantly higher cellular uptake efficiency, favorable endosome escape ability, and deep tumor penetration performance, leading to a higher anticancer efficiency, in comparison to free gelonin. This work provides a promising strategy and a generalized nanoplatform to efficiently deliver biofunctional proteins to unlock their therapeutic potential for cancer treatment. Full article
(This article belongs to the Special Issue Smart Drug Delivery Strategies Based on Porous Materials)
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11 pages, 2918 KiB  
Communication
Mesoporous Organosilica Nanoparticles with Tetrasulphide Bond to Enhance Plasmid DNA Delivery
by Yue Zhang, He Xian, Ekaterina Strounina, Kimberley S. Gunther, Matthew J. Sweet, Chen Chen, Chengzhong Yu and Yue Wang
Pharmaceutics 2023, 15(3), 1013; https://doi.org/10.3390/pharmaceutics15031013 - 22 Mar 2023
Cited by 2 | Viewed by 1643
Abstract
Cellular delivery of plasmid DNA (pDNA) specifically into dendritic cells (DCs) has provoked wide attention in various applications. However, delivery tools that achieve effective pDNA transfection in DCs are rare. Herein, we report that tetrasulphide bridged mesoporous organosilica nanoparticles (MONs) have enhanced pDNA [...] Read more.
Cellular delivery of plasmid DNA (pDNA) specifically into dendritic cells (DCs) has provoked wide attention in various applications. However, delivery tools that achieve effective pDNA transfection in DCs are rare. Herein, we report that tetrasulphide bridged mesoporous organosilica nanoparticles (MONs) have enhanced pDNA transfection performance in DC cell lines compared to conventional mesoporous silica nanoparticles (MSNs). The mechanism of enhanced pDNA delivery efficacy is attributed to the glutathione (GSH) depletion capability of MONs. Reduction of initially high GSH levels in DCs further increases the mammalian target of rapamycin complex 1 (mTORc1) pathway activation, enhancing translation and protein expression. The mechanism was further validated by showing that the increased transfection efficiency was apparent in high GSH cell lines but not in low GSH ones. Our findings may provide a new design principle of nano delivery systems where the pDNA delivery to DCs is important. Full article
(This article belongs to the Special Issue Smart Drug Delivery Strategies Based on Porous Materials)
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12 pages, 3415 KiB  
Communication
Smart Drug-Delivery System of Upconversion Nanoparticles Coated with Mesoporous Silica for Controlled Release
by Yanan Huang, Ziqing Du, Guochen Bao, Guocheng Fang, Matthew Cappadona, Lana McClements, Bernard E. Tuch, Hongxu Lu and Xiaoxue Xu
Pharmaceutics 2023, 15(1), 89; https://doi.org/10.3390/pharmaceutics15010089 - 27 Dec 2022
Cited by 5 | Viewed by 2141
Abstract
Drug-delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with controllable drug-release systems (DRSs) is still in its nascent stage. In this paper, we designed a two-way [...] Read more.
Drug-delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with controllable drug-release systems (DRSs) is still in its nascent stage. In this paper, we designed a two-way controlled drug-release system that can be promoted and prolonged, using the external stimulation of near-infrared light (NIR) and protein coating. A hierarchical nanostructure was fabricated using upconversion nanoparticles (UCNPs)—mesoporous silica as the core-shell structure with protein lysozyme coating. The mesoporous silica shell provides abundant pores for the loading of drug molecules and a specific type of photosensitive molecules. The morphology and the physical properties of the nanostructures were thoroughly characterized. The results exhibited the uniform core-shell nanostructures of ~four UCNPs encapsulated in one mesoporous silica nanoparticle. The core-shell nanoparticles were in the spherical shape with an average size of 200 nm, average surface area of 446.54 m2/g, and pore size of 4.6 nm. Using doxorubicin (DOX), a chemotherapy agent as the drug model, we demonstrated that a novel DRS with capacity of smart modulation to promote or inhibit the drug release under NIR light and protein coating, respectively. Further, we demonstrated the therapeutic effect of the designed DRSs using breast cancer cells. The reported novel controlled DRS with dual functionality could have a promising potential for chemotherapy treatment of solid cancers. Full article
(This article belongs to the Special Issue Smart Drug Delivery Strategies Based on Porous Materials)
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19 pages, 3743 KiB  
Article
A PEGylated Nanostructured Lipid Carrier for Enhanced Oral Delivery of Antibiotics
by Seyed Ebrahim Alavi, Urooj Bakht, Maedeh Koohi Moftakhari Esfahani, Hossein Adelnia, Seyed Hossein Abdollahi, Hasan Ebrahimi Shahmabadi and Aun Raza
Pharmaceutics 2022, 14(8), 1668; https://doi.org/10.3390/pharmaceutics14081668 - 11 Aug 2022
Cited by 7 | Viewed by 1939
Abstract
Antimicrobial resistance is a major concern for public health throughout the world that severely restricts available treatments. In this context, methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a high percentage of S. aureus infections and mortality. To overcome this challenge, nanoparticles are appropriate [...] Read more.
Antimicrobial resistance is a major concern for public health throughout the world that severely restricts available treatments. In this context, methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a high percentage of S. aureus infections and mortality. To overcome this challenge, nanoparticles are appropriate tools as drug carriers to improve the therapeutic efficacy and decrease the toxicity of drugs. In this study, a polyethylene glycol (PEG)ylated nanostructured lipid carrier (PEG-NLC) was synthesized to improve the oral delivery of trimethoprim/sulfamethoxazole (TMP/SMZ) for the treatment of MRSA skin infection in vitro and in vivo. The nanoformulation (PEG-TMP/SMZ-NLC) was synthesized with size and drug encapsulation efficiencies of 187 ± 9 nm and 93.3%, respectively, which could release the drugs in a controlled manner at intestinal pH. PEG-TMP/SMZ-NLC was found efficient in decreasing the drugs’ toxicity by 2.4-fold in vitro. In addition, the intestinal permeability of TMP/SMZ was enhanced by 54%, and the antibacterial effects of the drugs were enhanced by 8-fold in vitro. The results of the stability study demonstrated that PEG-TMP/SMZ-NLC was stable for three months. In addition, the results demonstrated that PEG-TMP/SMZ-NLC after oral administration could decrease the drugs’ side-effects such as renal and hepatic toxicity by ~5-fold in MRSA skin infection in Balb/c mice, while it could improve the antibacterial effects of TMP/SMZ by 3 orders of magnitude. Overall, the results of this study suggest that the application of PEGylated NLC nanoparticles is a promising approach to improving the oral delivery of TMP/SMZ for the treatment of MRSA skin infection. Full article
(This article belongs to the Special Issue Smart Drug Delivery Strategies Based on Porous Materials)
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24 pages, 6923 KiB  
Article
Ciprofloxacin-Loaded Titanium Nanotubes Coated with Chitosan: A Promising Formulation with Sustained Release and Enhanced Antibacterial Properties
by Soada Asadi, Bardia Mortezagholi, Alireza Hadizadeh, Vitaliy Borisov, Mohammad Javed Ansari, Hasan Shaker Majdi, Azizakhon Nishonova, Hossein Adelnia, Bahareh Farasati Far and Chaiyavat Chaiyasut
Pharmaceutics 2022, 14(7), 1359; https://doi.org/10.3390/pharmaceutics14071359 - 27 Jun 2022
Cited by 26 | Viewed by 2460
Abstract
Due to their high entrapment efficiency, anodized titanium nanotubes (TiO2-NTs) are considered effective reservoirs for loading/releasing strong antibiotics whose systemic administration is associated with diverse and severe side-effects. In this study, TiO2-NTs were synthesized by anodic oxidation of titanium [...] Read more.
Due to their high entrapment efficiency, anodized titanium nanotubes (TiO2-NTs) are considered effective reservoirs for loading/releasing strong antibiotics whose systemic administration is associated with diverse and severe side-effects. In this study, TiO2-NTs were synthesized by anodic oxidation of titanium foils, and the effects of electrolyte percentage and viscosity on their dimensions were evaluated. It was found that as the water content increased from 15 to 30%, the wall thickness, length, and inner diameter of the NTs increase from 5.9 to 15.8 nm, 1.56 to 3.21 µm, and 59 to 84 nm, respectively. Ciprofloxacin, a highly potent antibiotic, was loaded into TiO2-NTs with a high encapsulation efficiency of 93%, followed by coating with different chitosan layers to achieve a sustained release profile. The prepared formulations were characterized by various techniques, such as scanning electron microscopy, differential scanning calorimetry, and contact measurement. In vitro release studies showed that the higher the chitosan layer count, the more sustained the release. Evaluation of antimicrobial activity of the formulation against two endodontic species from Peptostreptococcus and Fusobacterium revealed minimum inhibitory concentrations (MICs) of 1 µg/mL for the former and the latter. To summarize, this study demonstrated that TiO2-NTs are promising reservoirs for drug loading, and that the chitosan coating provides not only a sustained release profile, but also a synergistic antibacterial effect. Full article
(This article belongs to the Special Issue Smart Drug Delivery Strategies Based on Porous Materials)
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19 pages, 3887 KiB  
Article
Stereomicroscope with Imaging Analysis: A Versatile Tool for Wetting, Gel Formation and Erosion Rate Determinations of Eutectic Effervescent Tablet
by Pornsit Chaiya, Siriporn Okonogi and Thawatchai Phaechamud
Pharmaceutics 2022, 14(6), 1280; https://doi.org/10.3390/pharmaceutics14061280 - 16 Jun 2022
Cited by 2 | Viewed by 1956
Abstract
Wettability, gel formation and erosion behaviors could influence the drug release pattern of solid dosage forms. Typically, these parameters are evaluated using a variety of techniques. Nonetheless, there has been no previous research on versatile tool development for evaluating several tablet characteristics with [...] Read more.
Wettability, gel formation and erosion behaviors could influence the drug release pattern of solid dosage forms. Typically, these parameters are evaluated using a variety of techniques. Nonetheless, there has been no previous research on versatile tool development for evaluating several tablet characteristics with a single tool. The aim of this study was to develop the versatile tool for measuring various physical properties of eutectic effervescent tablets and also investigate the relationship between these parameters with parameters from drug dissolution. Ibuprofen (IBU)-poloxamer 407 (P407) eutectic effervescent tablets were fabricated with a direct compression method. Their wetting properties, gel formation and erosion behaviors were investigated using a stereomicroscope with imaging analysis in terms of the liquid penetration distance, gel thickness and erosion boundary diameter, respectively. In addition, the dissolution rate (k) and disintegration time of eutectic effervescent tablets in 0.1 N HCl buffer pH 1.2 were also determined. Incorporation of P407 into the IBU tablet improved the tablet wetting properties with increasing liquid penetration distance under stereoscope. CO2 liberation from effervescent agents promoted tablet surface roughness from matrix erosion. The relationship between observed physical properties and disintegration and dissolution parameters suggested that the combination of erosion by effervescent agents and gel formation by P407 had a potential influence on dissolution enhancement of the formulation. Therefore, a developed stereomicroscope with an imaging analysis technique was exhibited as an alternative versatile tool for determining the wetting properties, gel formation and erosion behaviors of pharmaceutical solid dosage forms. Full article
(This article belongs to the Special Issue Smart Drug Delivery Strategies Based on Porous Materials)
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16 pages, 2968 KiB  
Article
β-Lactoglobulin-Modified Mesoporous Silica Nanoparticles: A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostate Cancer Cells
by Maedeh Koohi Moftakhari Esfahani, Seyed Ebrahim Alavi, Peter J. Cabot, Nazrul Islam and Emad L. Izake
Pharmaceutics 2022, 14(4), 884; https://doi.org/10.3390/pharmaceutics14040884 - 18 Apr 2022
Cited by 12 | Viewed by 2744
Abstract
The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility [...] Read more.
The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated β-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study. Full article
(This article belongs to the Special Issue Smart Drug Delivery Strategies Based on Porous Materials)
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16 pages, 4643 KiB  
Article
PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells
by Maedeh Koohi Moftakhari Esfahani, Seyed Ebrahim Alavi, Peter J. Cabot, Nazrul Islam and Emad L. Izake
Pharmaceutics 2021, 13(10), 1605; https://doi.org/10.3390/pharmaceutics13101605 - 02 Oct 2021
Cited by 24 | Viewed by 2895
Abstract
Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this [...] Read more.
Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study. Full article
(This article belongs to the Special Issue Smart Drug Delivery Strategies Based on Porous Materials)
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