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Keywords = prolonging/adjusted drug release

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13 pages, 1069 KiB  
Article
Cyclosporine Dissolution Test from a Lipid Dosage Form: Next Step Towards the Establishment of Release Method for Solid Lipid Microparticles
by Eliza Wolska, Patrycja Dudek and Małgorzata Sznitowska
Pharmaceutics 2025, 17(8), 1030; https://doi.org/10.3390/pharmaceutics17081030 - 8 Aug 2025
Viewed by 284
Abstract
Background: The release study is a standard tool for the development, evaluation, and control of dosage forms. In the case of traditional drug delivery systems, it is conducted in accordance with the established principles available in the European and American Pharmacopoeias or guidelines [...] Read more.
Background: The release study is a standard tool for the development, evaluation, and control of dosage forms. In the case of traditional drug delivery systems, it is conducted in accordance with the established principles available in the European and American Pharmacopoeias or guidelines proposed by registration agencies. The problem is the study of modern carriers, not yet described in compendia, which require adjustments to traditionally used methods. Objectives: The present study focuses on developing an optimal method for testing the release of cyclosporine (Cs, 0.5–4%) incorporated in solid lipid microparticles (SLM) dispersions (10%) intended for administration in the form of eye drops. This is a multicompartment lipid carrier that provides prolonged release of the active substance. Methods: Three methods of testing the release were compared: the dialysis bag method, the horizontal cells technique, and a method without a membrane. Results: During the analyses, the proper membrane was selected and the effect of the lysozyme enzyme on the release profile was analyzed. The effect of the composition of the acceptor fluid on the obtained results was also assessed. In the model without a membrane, up to 60% of the Cs was released within 30 min due to the burst effect. In horizontal chambers, no formulation released more than 14% of the Cs over 96 h, while at the same time, 60–70% of the Cs was released from the dialysis bag. Conclusions: Based on the obtained results, the dialysis bag method was selected to study the release of Cs from SLM without the need to use multicomponent artificial tear fluid as an acceptor medium. Full article
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15 pages, 6551 KiB  
Article
Effects of Chitosan on Drug Load and Release for Cisplatin–Hydroxyapatite–Gelatin Composite Microspheres
by Meng-Ying Wu, I-Fang Kao and Shiow-Kang Yen
Polymers 2025, 17(11), 1485; https://doi.org/10.3390/polym17111485 - 27 May 2025
Viewed by 675
Abstract
Cisplatin, a widely used chemotherapeutic agent, is limited by its poor bioavailability, rapid systemic clearance, and severe side effects. To overcome these limitations, hydroxyapatite–gelatin composite microspheres were developed to improve drug entrapment efficiency (DEE) and provide sustained drug release. Various formulations were prepared [...] Read more.
Cisplatin, a widely used chemotherapeutic agent, is limited by its poor bioavailability, rapid systemic clearance, and severe side effects. To overcome these limitations, hydroxyapatite–gelatin composite microspheres were developed to improve drug entrapment efficiency (DEE) and provide sustained drug release. Various formulations were prepared by incorporating chitosan either by mixing once or through a sequential coating strategy. By adjusting the loading procedure, the DEE increased from 58% to 99%. The composite microsphere effectively controlled the total drug release duration, extending it from one month to over 5 months. Moreover, the MTT assay demonstrated that all samples effectively inhibited cell growth, with cell viability reduced to less than 20% after 2 weeks of experimentation. These findings demonstrate that the sequential chitosan coating method offers superior drug entrapment and prolonged release compared to mixing chitosan once, exhibiting its potential as a sustained drug delivery system for cancer treatment. Full article
(This article belongs to the Special Issue Polymer Composites for Biomedical Applications)
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25 pages, 5167 KiB  
Article
Optimizing Thermoresponsive and Bioadhesive Systems for Local Application of Erythrosine
by Igor Alves Endrice, Sandy Aline Forastieri Gerarduzzi, Mariana Carla de Oliveira, Marcos Luciano Bruschi and Jéssica Bassi da Silva
Colorants 2025, 4(1), 5; https://doi.org/10.3390/colorants4010005 - 5 Feb 2025
Viewed by 2895
Abstract
Photodynamic therapy (PDT) is a light-activated chemical reaction used for the selective destruction of tissue. For this, various colorants may be applied, such as erythrosine (ERI), a dye already approved by the Food and Drug Administration (FDA) for various purposes. Although promising for [...] Read more.
Photodynamic therapy (PDT) is a light-activated chemical reaction used for the selective destruction of tissue. For this, various colorants may be applied, such as erythrosine (ERI), a dye already approved by the Food and Drug Administration (FDA) for various purposes. Although promising for PDT, ERI has a high hydrophilic profile that impacts its activity. To solve this, the combination of ERI with thermoresponsive and bioadhesive polymers may prove effective. Bio/mucoadhesive and thermoresponsive systems have attracted increasing interest in the development of novel pharmaceutical formulations for topical applications due to their ability to improve adhesion to the mucosa and prolong the residence time at the application site. In this study, systems based on poloxamer 407 (P407) in combination with cellulose derivatives (HPMC and NaCMC) were optimized, aiming at the topical release of ERI for PDT. The results demonstrated that the formulations containing low concentrations of cellulose derivatives exhibited greater adhesiveness and consistency at physiological temperature (37 °C), favoring the maintenance of the system at the application site. Regarding the gelation temperature (Tsol/gel), the formulations displayed values close to body temperature. The formulations with NaCMC showed a slightly higher Tsol/gel compared to HPMC ones, but it was adjustable by the polymer concentration. The addition of ERI influenced the mechanical and adhesive properties of the systems. In formulations containing HPMC, high concentrations of ERI increased bio/mucoadhesiveness, while in systems with NaCMC, the presence of ERI reduced this property. In both cases, the formulations maintained high consistency at 37 °C, contributing to the control of the active release at the application site. Rheological analysis revealed non-Newtonian behavior in all formulations, with greater consistency and elasticity at high temperatures. P407 was mainly responsible for the thermoresponsive transition from sol to gel, conferring desirable characteristics for topical application. Photodynamic activity was relevant in both formulations containing NaCMC and HPMC, which demonstrated greater capacity for degrading uric acid under light exposure. These systems are promising for the controlled release of drugs in photodynamic therapy, providing prolonged retention in the target tissue and maximizing the therapeutic efficacy of ERI. Full article
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27 pages, 9145 KiB  
Article
Application of Hydrophilic Polymers to the Preparation of Prolonged-Release Minitablets with Bromhexine Hydrochloride and Bisoprolol Fumarate
by Agata Grzejdziak, Witold Brniak, Olaf Lengier, Justyna Anna Żarek, Dziyana Hliabovich and Aleksander Mendyk
Pharmaceutics 2024, 16(9), 1153; https://doi.org/10.3390/pharmaceutics16091153 - 30 Aug 2024
Cited by 1 | Viewed by 1634
Abstract
Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification [...] Read more.
Minitablets have been extensively studied in recent years as a convenient pediatric form because they allow successful administration even in very young children. Their advantages include easy dose adjustment by multiplication of single units as well as the possibility of drug release modification by coating or forming matrix systems. The aim of this study was to demonstrate the possibility of the formulation of prolonged-release minitablets with bromhexine hydrochloride (BHX) and bisoprolol fumarate (BFM) dedicated to pediatric patients. Minitablets with 3 mm diameter and 15 mg mass, containing 1 mg of active substance in 1 unit, were prepared by direct compression with hydroxypropyl methylcellulose (HPMC) of different grades, methylcellulose, sodium alginate, or polyvinyl alcohol (PVA) as a sustained-release polymer. Different amounts of polymers and different compression forces were evaluated. Analysis of minitablets included their uniformity, hardness, and dissolution tests. The kinetics of drug substance release were analyzed with dedicated software. The prepared minitablets met the pharmacopeial requirements with respect to the uniformity of mass and content. The compressibility of BFM was significantly better than that of BHX, yet all minitablets had good mechanical properties. Dissolution studies showed a strong relationship between the type of polymer and its amount in the mass of a tablet and the dissolution rate. Prolonged release of up to 8 h was achieved when HPMC of 4000 cP viscosity was used in the amount of 30% to 80%. Sodium alginate in the amount of 50% was also effective in prolonging dissolution, but PVA was much less effective. Studies on the release kinetics showed that dissolution from prolonged-release minitablets with BHX fit the best to Hopfenberg or Hixson–Crowell models, while in the case of BFM, the best fit was found for Hopfenberg or Korsmeyer–Peppas models. Full article
(This article belongs to the Special Issue Advanced Pharmaceutical Excipients Used in Solid Dosage Forms)
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13 pages, 4419 KiB  
Article
Assembled pH-Responsive Gastric Drug Delivery Systems Based on 3D-Printed Shells
by Haoye Bei, Pingping Zhao, Lian Shen, Qingliang Yang and Yan Yang
Pharmaceutics 2024, 16(6), 717; https://doi.org/10.3390/pharmaceutics16060717 - 27 May 2024
Cited by 2 | Viewed by 2590
Abstract
Gastric acid secretion is closely associated with the development and treatment of chronic gastritis, gastric ulcers, and reflux esophagitis. However, gastric acid secretion is affected by complex physiological and pathological factors, and real-time detection and control are complicated and expensive. A gastric delivery [...] Read more.
Gastric acid secretion is closely associated with the development and treatment of chronic gastritis, gastric ulcers, and reflux esophagitis. However, gastric acid secretion is affected by complex physiological and pathological factors, and real-time detection and control are complicated and expensive. A gastric delivery system for antacids and therapeutics in response to low pH in the stomach holds promise for smart and personalized treatment of stomach diseases. In this study, pH-responsive modular units were used to assemble various modular devices for self-regulation of pH and drug delivery to the stomach. The modular unit with a release window of 50 mm2 could respond to pH and self-regulate within 10 min, which is related to its downward floatation and internal gas production. The assembled devices could stably float downward in the medium and detach sequentially at specific times. The assembled devices loaded with antacids exhibited smart pH self-regulation under complex physiological and pathological conditions. In addition, the assembled devices loaded with antacids and acid suppressors could multi-pulse or prolong drug release after rapid neutralization of gastric acid. Compared with traditional coating technology, 3D printing can print the shell layer by layer, flexibly adjust the internal and external structure and composition, and assemble it into a multi-level drug release system. Compared with traditional coating, 3D-printed shells have the advantage of the flexible adjustment of internal and external structure and composition, and are easy to assemble into a complex drug delivery system. This provides a universal and flexible strategy for the personalized treatment of diseases with abnormal gastric acid secretion, especially for delivering acid-unstable drugs. Full article
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13 pages, 1682 KiB  
Article
Multi-Armed Star-Shaped Block Copolymers of Poly(ethylene glycol)-Poly(furfuryl glycidol) as Long Circulating Nanocarriers
by Yasuhiro Nakagawa, Kotaro Ushidome, Keita Masuda, Kazunori Igarashi, Yu Matsumoto, Tatsuya Yamasoba, Yasutaka Anraku, Madoka Takai and Horacio Cabral
Polymers 2023, 15(12), 2626; https://doi.org/10.3390/polym15122626 - 9 Jun 2023
Cited by 3 | Viewed by 2545
Abstract
Multi-arm star-shaped block copolymers with precisely tuned nano-architectures are promising candidates for drug delivery. Herein, we developed 4- and 6-arm star-shaped block copolymers consisting of poly(furfuryl glycidol) (PFG) as the core-forming segments and biocompatible poly(ethylene glycol) (PEG) as the shell-forming blocks. The polymerization [...] Read more.
Multi-arm star-shaped block copolymers with precisely tuned nano-architectures are promising candidates for drug delivery. Herein, we developed 4- and 6-arm star-shaped block copolymers consisting of poly(furfuryl glycidol) (PFG) as the core-forming segments and biocompatible poly(ethylene glycol) (PEG) as the shell-forming blocks. The polymerization degree of each block was controlled by adjusting the feeding ratio of a furfuryl glycidyl ether and ethylene oxide. The size of the series of block copolymers was found to be less than 10 nm in DMF. In water, the polymers showed sizes larger than 20 nm, which can be related to the association of the polymers. The star-shaped block copolymers effectively loaded maleimide-bearing model drugs in their core-forming segment with the Diels–Alder reaction. These drugs were rapidly released upon heating via a retro Diels–Alder step. When the star-shaped block copolymers were injected intravenously in mice, they showed prolonged blood circulation, with more than 80% of the injected dose remaining in the bloodstream at 6 h after intravenous injection. These results indicate the potential of the star-shaped PFG-PEG block copolymers as long-circulating nanocarriers. Full article
(This article belongs to the Special Issue Bioactivated Polymers for Nanomedicine)
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13 pages, 2374 KiB  
Article
Comparison between the Astaxanthin Release Profile of Mesoporous Bioactive Glass Nanoparticles (MBGNs) and Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)/MBGN Composite Microspheres
by Arturo E. Aguilar-Rabiela, Shahin Homaeigohar, Eduin I. González-Castillo, Mirna L. Sánchez and Aldo R. Boccaccini
Polymers 2023, 15(11), 2432; https://doi.org/10.3390/polym15112432 - 24 May 2023
Cited by 4 | Viewed by 2346
Abstract
In recent years, composite biomaterials have attracted attention for drug delivery applications due to the possibility of combining desired properties of their components. However, some functional characteristics, such as their drug release efficiency and likely side effects, are still unexplored. In this regard, [...] Read more.
In recent years, composite biomaterials have attracted attention for drug delivery applications due to the possibility of combining desired properties of their components. However, some functional characteristics, such as their drug release efficiency and likely side effects, are still unexplored. In this regard, controlled tuning of the drug release kinetic via the precise design of a composite particle system is still of high importance for many biomedical applications. This objective can be properly fulfilled through the combination of different biomaterials with unequal release rates, such as mesoporous bioactive glass nanoparticles (MBGN) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) microspheres. In this work, MBGNs and PHBV-MBGN microspheres, both loaded with Astaxanthin (ASX), were synthesised and compared in terms of ASX release kinetic, ASX entrapment efficiency, and cell viability. Moreover, the correlation of the release kinetic to phytotherapeutic efficiency and side effects was established. Interestingly, there were significant differences between the ASX release kinetic of the developed systems, and cell viability differed accordingly after 72 h. Both particle carriers effectively delivered ASX, though the composite microspheres exhibited a more prolonged release profile with sustained cytocompatibility. The release behaviour could be fine-tuned by adjusting the MBGN content in the composite particles. Comparatively, the composite particles induced a different release effect, implying their potential for sustained drug delivery applications. Full article
(This article belongs to the Special Issue Biomedical Applications of Polymeric Materials)
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22 pages, 1634 KiB  
Review
Chitosan-Based Polymer Blends for Drug Delivery Systems
by Malkiet Kaur, Ameya Sharma, Vivek Puri, Geeta Aggarwal, Paramjot Maman, Kampanart Huanbutta, Manju Nagpal and Tanikan Sangnim
Polymers 2023, 15(9), 2028; https://doi.org/10.3390/polym15092028 - 25 Apr 2023
Cited by 37 | Viewed by 6649
Abstract
Polymers have been widely used for the development of drug delivery systems accommodating the regulated release of therapeutic agents in consistent doses over a long period, cyclic dosing, and the adjustable release of both hydrophobic and hydrophilic drugs. Nowadays, polymer blends are increasingly [...] Read more.
Polymers have been widely used for the development of drug delivery systems accommodating the regulated release of therapeutic agents in consistent doses over a long period, cyclic dosing, and the adjustable release of both hydrophobic and hydrophilic drugs. Nowadays, polymer blends are increasingly employed in drug development as they generate more promising results when compared to those of homopolymers. This review article describes the recent research efforts focusing on the utilization of chitosan blends with other polymers in an attempt to enhance the properties of chitosan. Furthermore, the various applications of chitosan blends in drug delivery are thoroughly discussed herein. The literature from the past ten years was collected using various search engines such as ScienceDirect, J-Gate, Google Scholar, PubMed, and research data were compiled according to the various novel carrier systems. Nanocarriers made from chitosan and chitosan derivatives have a positive surface charge, which allows for control of the rate, duration, and location of drug release in the body, and can increase the safety and efficacy of the delivery system. Recently developed nanocarriers using chitosan blends have been shown to be cost-effective, more efficacious, and prolonged release carriers that can be incorporated into suitable dosage forms. Full article
(This article belongs to the Special Issue Natural Polymers: Isolation, Modification, and Applications)
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13 pages, 3284 KiB  
Review
Preparation and Biomedical Applications of Cucurbit[n]uril-Based Supramolecular Hydrogels
by Ruihan Gao, Qingmei Ge, Hang Cong, Yunqian Zhang and Jianglin Zhao
Molecules 2023, 28(8), 3566; https://doi.org/10.3390/molecules28083566 - 19 Apr 2023
Cited by 6 | Viewed by 3632
Abstract
The cucurbit[n]uril supramolecular hydrogels are driven by weak intermolecular interactions, of which exhibit good stimuli responsiveness and excellent self-healing properties. According to the composition of the gelling factor, supramolecular hydrogels comprise Q[n]-cross-linked small molecules and Q[n]-cross-linked polymers. According to different driving forces, hydrogels [...] Read more.
The cucurbit[n]uril supramolecular hydrogels are driven by weak intermolecular interactions, of which exhibit good stimuli responsiveness and excellent self-healing properties. According to the composition of the gelling factor, supramolecular hydrogels comprise Q[n]-cross-linked small molecules and Q[n]-cross-linked polymers. According to different driving forces, hydrogels are driven by the outer-surface interaction, the host–guest inclusion interaction, and the host–guest exclusion interaction. Host–guest interactions are widely used in the construction of self-healing hydrogels, which can spontaneously recover after being damaged, thereby prolonging their service life. The smart Q[n]s-based supramolecular hydrogel composed is a kind of adjustable and low-toxicity soft material. By designing the structure of the hydrogel or modifying the fluorescent properties, etc., it can be widely used in biomedicine. In this review, we mainly focus on the preparation of Q[n]-based hydrogels and their biomedical applications including cell encapsulation for biocatalysis, biosensors for high sensitivity, 3D printing for potential tissue engineering, drug release for sustained delivery, and interfacial adhesion for self-healing materials. In addition, we also presented the current challenges and prospects in this field. Full article
(This article belongs to the Special Issue Preparation and Applications of Hydrogels)
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20 pages, 6503 KiB  
Article
Montmorillonite–Rifampicin Nanohybrid for pH-Responsive Release of the Tuberculostatic
by Elmar Damasceno Junior, Raquel de Melo Barbosa, Rita de Cássia Dantas da Silva, Felipe dos Santos Costa, Djalma Ribeiro da Silva, César Viseras, Luana Perioli and Nedja Suely Fernandes
Pharmaceutics 2023, 15(2), 512; https://doi.org/10.3390/pharmaceutics15020512 - 3 Feb 2023
Cited by 5 | Viewed by 2413
Abstract
The present work describes the development of a hybrid and pH-responsive system for rifampicin using the clay mineral ‘montmorillonite’ as a nanocarrier. The influence of operational variables on the drug incorporation process was evaluated using 24 factorial designs. Under optimized conditions, the [...] Read more.
The present work describes the development of a hybrid and pH-responsive system for rifampicin using the clay mineral ‘montmorillonite’ as a nanocarrier. The influence of operational variables on the drug incorporation process was evaluated using 24 factorial designs. Under optimized conditions, the experiment allowed an incorporated drug dose equivalent to 98.60 ± 1.21 mg/g. Hybrid systems were characterized by different characterization techniques (FTIR, XRD, TGA, DSC, and SEM) to elucidate the mechanism of interaction between the compounds used. Through in vitro release studies, it was possible to verify the efficacy of the pH-dependent system obtained, with approximately 70% of the drug released after sixteen hours in simulated intestinal fluid. The adjustment of the experimental release data to the theoretical model of Higuchi and Korsmeyer–Peppas indicated that the release of rifampicin occurs in a prolonged form from montmorillonite. Elucidation of the interactions between the drug and this raw clay reinforces its viability as a novel carrier to develop an anti-TB/clay hybrid system with good physical and chemical stability. Full article
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14 pages, 3261 KiB  
Article
Use of Self-Assembled Colloidal Prodrug Nanoparticles for Controlled Drug Delivery of Anticancer, Antifibrotic and Antibacterial Mitomycin
by Mohamed M. Abdelghafour, Ágota Deák, Diána Szabó, Imre Dékány, László Rovó and László Janovák
Int. J. Mol. Sci. 2022, 23(12), 6807; https://doi.org/10.3390/ijms23126807 - 18 Jun 2022
Cited by 13 | Viewed by 2926
Abstract
Herein we present the synthesis of a polymeric prodrug nanomaterial capable of spontaneous, self-assembled nanoparticle formation and of the conjugation (encapsulation) of drugs with amino and/or carboxyl and/or hydroxyl groups via ester and/or amide linkage. Mitomycin C (MMC) a versatile drug with antibiotic, [...] Read more.
Herein we present the synthesis of a polymeric prodrug nanomaterial capable of spontaneous, self-assembled nanoparticle formation and of the conjugation (encapsulation) of drugs with amino and/or carboxyl and/or hydroxyl groups via ester and/or amide linkage. Mitomycin C (MMC) a versatile drug with antibiotic, antibacterial and antineoplastic properties, was used to prove this concept. The in vitro drug release experiments showed a fast release for the pure MMC (k = 49.59 h−n); however, a significantly lower MMC dissolution rate (k = 2.25, 1.46, and 1.35 h−n) was obtained for the nanoparticles with increased cross-link density (3, 10, 21%). The successful modification and conjugation reactions were confirmed using FTIR and EDX measurements, while the mucoadhesive properties of the self-assembled particles synthesized in a simple one-pot reaction were proved by rheological measurement. The prepared biocompatible polymeric prodrugs are very promising and applicable as a drug delivery system (DDS) and useful in the area of cancer treatment. Full article
(This article belongs to the Special Issue Biomaterials and Regenerative Medicine)
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14 pages, 3560 KiB  
Article
Effects of Injection Volume and Route of Administration on Dolutegravir In Situ Forming Implant Pharmacokinetics
by Jordan B. Joiner, Jasmine L. King, Roopali Shrivastava, Sarah Anne Howard, Mackenzie L. Cottrell, Angela D. M. Kashuba, Paul A. Dayton and Soumya Rahima Benhabbour
Pharmaceutics 2022, 14(3), 615; https://doi.org/10.3390/pharmaceutics14030615 - 11 Mar 2022
Cited by 7 | Viewed by 4071
Abstract
Due to the versatility of the in situ forming implant (ISFI) drug delivery system, it is crucial to understand the effects of formulation parameters for clinical translation. We utilized ultrasound imaging and pharmacokinetics (PK) in mice to understand the impact of administration route, [...] Read more.
Due to the versatility of the in situ forming implant (ISFI) drug delivery system, it is crucial to understand the effects of formulation parameters for clinical translation. We utilized ultrasound imaging and pharmacokinetics (PK) in mice to understand the impact of administration route, injection volume, and drug loading on ISFI formation, degradation, and drug release in mice. Placebo ISFIs injected subcutaneously (SQ) with smaller volumes (40 μL) exhibited complete degradation within 30–45 days, compared to larger volumes (80 μL), which completely degraded within 45–60 days. However, all dolutegravir (DTG)-loaded ISFIs along the range of injection volumes tested (20–80 μL) were present at 90 days post-injection, suggesting that DTG can prolong ISFI degradation. Ultrasound imaging showed that intramuscular (IM) ISFIs flattened rapidly post administration compared to SQ, which coincides with the earlier Tmax for drug-loaded IM ISFIs. All mice exhibited DTG plasma concentrations above four times the protein-adjusted 90% inhibitory concentration (PA-IC90) throughout the entire 90 days of the study. ISFI release kinetics best fit to zero order or diffusion-controlled models. When total administered dose was held constant, there was no statistical difference in drug exposure regardless of the route of administration or number of injections. Full article
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13 pages, 2750 KiB  
Article
Affinity-Controlled Double-Network Hydrogel Facilitates Long-Term Release of Anti-Human Papillomavirus Protein
by Chenjia Zhao, Jingyuan Ji, Tianjun Yin, Jing Yang, Yuan Pang and Wei Sun
Biomedicines 2021, 9(10), 1298; https://doi.org/10.3390/biomedicines9101298 - 23 Sep 2021
Cited by 16 | Viewed by 3920
Abstract
Hydrogels have recently received attention as delivery carriers owing to their good biocompatibility and structural similarity to natural extracellular matrices. However, the utilization of traditional single-network (SN) hydrogels is limited by poor mechanical properties and burst drug release. Therefore, we developed a novel [...] Read more.
Hydrogels have recently received attention as delivery carriers owing to their good biocompatibility and structural similarity to natural extracellular matrices. However, the utilization of traditional single-network (SN) hydrogels is limited by poor mechanical properties and burst drug release. Therefore, we developed a novel double-network (DN) hydrogel, which employs an alginate (ALG)/polyethylene glycol diacrylate (PEGDA) network to adjust the mechanical strength and a positively charged monomer AETAC (2-(acryloyloxy)ethyl]trimethyl-ammonium chloride) to regulate the release curve of the electronegative anti-human papillomavirus (HPV) protein (bovine β-lactoglobulin modified with 3-hydroxyphthalic anhydride) based on an affinity-controlled delivery mechanism. The results show that the double-network hydrogel strongly inhibits the burst release, and the burst release amount is about one-third of that of the single-network hydrogel. By changing the concentration of the photoinitiator, the mechanical strength of the DN hydrogels can be adjusted to meet the stiffness requirements for various tissues within the range of 0.71 kPa to 10.30 kPa. Compared with the SN hydrogels, the DN hydrogels exhibit almost twice the mechanical strength and have smaller micropores. Cytotoxicity tests indicated that these SN and DN hydrogels were not cytotoxic with the result of over 100% relative proliferation rate of the HUVECs. Furthermore, DN hydrogels can significantly alleviate the burst release of antiviral proteins and prolong the release time to more than 14 days. Finally, we utilized digital light processing (DLP) technology to verify the printability of the DN hydrogel. Our study indicates that ALG/PEGDA-AETAC DN hydrogels could serve as platforms for delivering proteins and show promise for diverse tissue engineering applications. Full article
(This article belongs to the Special Issue Hydrogels for Biomedical Application)
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22 pages, 19554 KiB  
Article
Three-Dimensional Printing of Curcumin-Loaded Biodegradable and Flexible Scaffold for Intracranial Therapy of Glioblastoma Multiforme
by Ruixiu Li, Yunmei Song, Paris Fouladian, Mohammad Arafat, Rosa Chung, Jarrod Kohlhagen and Sanjay Garg
Pharmaceutics 2021, 13(4), 471; https://doi.org/10.3390/pharmaceutics13040471 - 31 Mar 2021
Cited by 32 | Viewed by 4089
Abstract
A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable [...] Read more.
A novel drug delivery system preventing Glioblastoma multiforme (GBM) recurrence after resection surgery is imperatively required to overcome the mechanical limitation of the current local drug delivery system and to offer personalised treatment options for GBM patients. In this study, 3D printed biodegradable flexible porous scaffolds were developed via Fused Deposition Modelling (FDM) three-dimensional (3D) printing technology for the local delivery of curcumin. The flexible porous scaffolds were 3D printed with various geometries containing 1, 3, 5, and 7% (w/w) of curcumin, respectively, using curcumin-loaded polycaprolactone (PCL) filaments. The scaffolds were characterised by a series of characterisation studies and in vitro studies were also performed including drug release study, scaffold degradation study, and cytotoxicity study. The curcumin-loaded PCL scaffolds displayed versatile spatiotemporal characteristics. The polymeric scaffolds obtained great mechanical flexibility with a low tensile modulus of less than 2 MPa, and 4 to 7-fold ultimate tensile strain, which can avoid the mechanical mismatch problem of commercially available GLIADEL wafer with a further improvement in surgical margin coverage. In vitro release profiles have demonstrated the sustained release patterns of curcumin with adjustable release amounts and durations up to 77 h. MTT study has demonstrated the great cytotoxic effect of curcumin-loaded scaffolds against the U87 human GBM cell line. Therefore, 3D printed curcumin-loaded scaffold has great promise to provide better GBM treatment options with its mechanical flexibility and customisability to match individual needs, preventing post-surgery GBM recurrence and eventually prolonging the life expectancy of GBM patients. Full article
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21 pages, 9439 KiB  
Article
Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading
by Gordana Stanojević, Djordje Medarević, Ivana Adamov, Nikola Pešić, Jovana Kovačević and Svetlana Ibrić
Molecules 2021, 26(1), 111; https://doi.org/10.3390/molecules26010111 - 29 Dec 2020
Cited by 48 | Viewed by 4564
Abstract
Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by [...] Read more.
Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by varying the tablet thickness and the drug loading, as well as to develop artificial neural network (ANN) predictive models for atomoxetine (ATH) release rate from DLP 3D-printed tablets. Photoreactive mixtures were comprised of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 in a constant ratio of 3:1, water, photoinitiator and ATH as a model drug whose content was varied from 5% to 20% (w/w). Designed 3D models of cylindrical shape tablets were of constant diameter, but different thickness. A series of tablets with doses ranging from 2.06 mg to 37.48 mg, exhibiting immediate- and modified-release profiles were successfully fabricated, confirming the potential of this technology in manufacturing dosage forms on demand, with the possibility to adjust the dose and release behavior by varying drug loading and dimensions of tablets. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and microscopic analysis showed that ATH remained in a crystalline form in tablets, while FTIR spectroscopy confirmed that no interactions occurred between ATH and polymers. Full article
(This article belongs to the Special Issue 3D Printing for Chemical, Pharmaceutical, and Biological Applications)
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