Prolonged Drug Release Research Articles

Development and Characterization of Oral Efavirenz-Loaded Nanostructured Lipid Carriers and Their Optimization with Box-Behnken Design Approach for the Neurological Disorder.

To enhance brain delivery of efavirenz (EFV), optimized nanostructured lipid carriers (NLCs) were developed using a melt-emulsification technique and probe sonication. Box-Behnken design was chosen to systematically analyze the effects of variables on formulation outcomes, enabling efficient optimization with fewer experimental trials. This selection helped to improve the formulation by allowing us to refine key characteristics such as particle size, entrapment efficiency, and polydispersity index (PDI). The optimized EFV-NLCs had a mean particle size of 91.41 ± 7.90 nm, a PDI of 0.28 ± 0.04, a zeta potential of -17 mV, an entrapment efficiency of 85 ± 7%, and a drug loading of 14 ± 1%. Transmission electron microscopy confirmed that the EFV-NLCs were spherical with uniform size distribution. In vitro release tests showed prolonged drug release, with release rates ranging from 63.09 ± 2.76% to 84.43 ± 4.24% at pH 1.2 and 87.66 ± 6.31% to 92.56 ± 1.48% at pH 6.8. This was significantly better than the EFV suspension, which showed moderate and unsustainable release rates over 8 h. Furthermore, dissolution studies in both fasted and fed state simulated-intestinal-fluids (FaSSIF and FeSSIF) over 6 h revealed that % cumulative drug release was significantly higher in FeSSIF (94.06 ± 1.62%) compared with FaSSIF (65.21 ± 3.95%), indicating enhanced absorption in the presence of food. In vitro gut permeation studies revealed that EFV-NLCs had a 2.05-fold higher drug permeability than the suspension. These findings suggest that EFV-NLCs are promising for targeted brain delivery, are safe for oral administration, and could be instrumental in managing neuro-acquired immunodeficiency syndrome.

Preparation, Characterization, and Drug Release of Electrospun Core‐Shell Structured Hyaluronic Acid‐Bovine Serum Albumin/Poly(ε‐Caprolactone) Nanofiber Membranes

ABSTRACTAlbumin has broad applications in tissue engineering, yet challenges remain in maintaining activity, loading capacity, and controlled release. In this study, we employed electrospinning to fabricate protein‐polysaccharide/poly(ε‐caprolactone) (PCL) nanofibers with a core‐shell structure. High‐magnification projection microscopy characterized the spinnability of hyaluronic acid‐bovine serum albumin (HyA‐BSA) solution. Scanning electron microscopy and high‐magnification projection microscopy demonstrated that the nanofibers had uniform diameter and internal structure, with Fourier‐transform infrared spectroscopy confirming the successful encapsulation of HyA‐BSA within PCL fibers. X‐ray diffraction indicated that the crystallite size of PCL decreased with increasing Span80 and HyA‐BSA content. Tensile and water contact angle tests revealed improvements in the flexibility and wettability of the nanofibers. In vitro drug tests indicated that the BSA loading and release rate could be modulated by varying Span80 and HyA‐BSA concentrations, with a total release time exceeding 30 days. Overall, this research enables prolonged drug release and offers new insights for protein encapsulation.

Development of propranolol loaded SLN for transdermal delivery: in-vitro characterization and skin deposition studies.

The study aimed to formulate solid lipid nanoparticles (SLNs) for the transdermal delivery of PPL to improve skin retention and efficacy. The particle size distribution of SLNs was determined and the morphology of SLNs was also analyzed by SEM. In-vitro, ex-vivo and in vivo evaluations were done for PPL loaded SLN. The safety of drug delivery systems was assayed using MTT test. The results indicated successful encapsulation of PPL in SLNs (59.38%), which exhibited a spherical shape and smooth surface. Compared to PPL solution, SLNs demonstrated a prolonged drug release profile in vitro. Stability tests over three months showed no significant changes in entrapment efficiency or size distribution. Enhanced permeation through shed snake and rat skin was observed with SLNs compared to the PPL solution. Ex-vivo and in vivo studies confirmed that PPL-loaded SLNs significantly increased drug content in the skin. Importantly, the SLNs displayed biocompatibility, as no significant cytotoxic effects were noted, and they were nonirritating to rat skin. To the best of our knowledge, this is the first study that indicates SLNs can be considered as a promising nanocarriers for transdermal delivery of PPL.

Advancements and Prospects in Nanorobotic Applications for Ophthalmic Therapy.

This study provides a bibliometric and bibliographic review of emerging applications of micro- and nanotechnology in treating ocular diseases, with a primary focus on glaucoma. We aim to identify key research trends and analyze advancements in devices and drug delivery systems for ocular treatments. The methodology involved analyzing 385 documents indexed on the Web of Science using tools such as VOSviewer and Bibliometrix. The results show a marked increase in scientific output, highlighting prominent authors and institutions, with England leading in the field. Key findings suggest that nanotechnology holds the potential to address the limitations of conventional treatments, including low ocular bioavailability and adverse side effects. Nanoparticles, nanovesicles, and polymer-based systems appear promising for prolonged and controlled drug release, potentially offering enhanced therapeutic efficacy. In conclusion, micro- and nanotechnology could transform ocular disease treatment, although challenges remain concerning the biocompatibility and scalability of these devices. Further clinical studies are necessary to establish these innovations within the therapeutic context of ophthalmology.

Novel hybrid system based on carboxymethyl chitosan hydrogel encapsulating drug loaded nanoparticles for prolonged release of Vancomycin in the treatment of bacterial infection.

Current bacterial infections clinical treatments, such as intravenous antibiotic administration and local injection, suffer from short action duration, repeated administrations, and severe cell toxicity. To address these limitations, it is imperative to develop sustained drug release system with prolonged antimicrobial effects. In this work, a hybrid system was prepared using EDC/NHS catalyzed crosslinking-based carboxymethyl chitosan (CMCS) hydrogel as a carrier to encapsulate biodegradable nanoparticles (NPs) loaded with vancomycin, an efficient antibacterial drug. First, ring opening polymerization of L-lactide or L-lactide/glycolide mixture was performed in the presence of poly(ethylene glycol) (PEG) to yield PEG-PLA or PEG-PLGA block copolymers. Vancomycin was loaded in PEG-PLA or PEG-PLGA NPs using double emulsion method. Drug-loaded NPs were then encapsulated in the CMCS hydrogel. Drug release from NPs, CMCS hydrogel and hybrid NPs-hydrogel systems was performed, and release kinetics were analyzed using Korsmeyer-Peppas model. The established hybrid system exhibited prolonged drug release without burst release. Finally, the biocompatibility of the hybrid system was evidenced by the MTT, hemolysis, dynamic clotting time, and zebrafish embryotoxicity tests. Last but not least, the hybrid system displayed outstanding long-lasting antimicrobial activity as shown by co-culture with Monoclonal S. aureus, thus suggesting great potential for applications in bacterial infection treatment.

FORMULATION OF TOLNOFTATE LOADED CUBOSOMES FOR EFFECTIVE TRANSDERMAL DELIVERY: AN IN VITRO AND EX-VIVO STUDY

Objective: The novel topical application has several benefits over traditional dosing forms, such as preventing gastrointestinal discomfort, lowering liver drug metabolism, and increasing medication bioavailability. Tolnaftate is used as potential anti-fungal agent various fungal infections. Methods: The cubosomes were formulated by emulsification technique using probe sonicator. The formulation was optimized using different concentrations of glyceryl monooleate and poloxamer 407. Results: The formed cubosomes dispersion was subjected to entrapment efficiency, surface morphology, particle size, in vitro release, anti-fungal study and ex-vivo study. The improved formulation was then transformed to a cubosomal hydrogel by the addition of carbopol 934. The average particle size of the optimised cubosomes was 208.0 nm. Zeta potential has been found to be 49.8 mV, with an entrapment efficiency of almost 90.0%. The drug steady-state flux (Jss) values for Tolnaftate Cubosomal formulation, marketed formulation, and plain drug gel were nearly 11.98, 10.23, and 10.06 g/cm2. h. As compared to standard marketed preparation, the cubosome-loaded formulation demonstrated enhanced penetration, extended deposition, and prolonged drug release. Conclusion: The drug had low solubility and permeability; it was overcome and produced superior outcomes in the form of cubosomes, which considerably increased the drug's solubility and permeability.

Liposomal Drug Delivery: Comparative Kinetics, Efficacy, and Applications in Targeted Therapeutics

During the Second World War, in order to reduce infections in soldiers wounds, nurses had to inject the injured with multiple shots of penicillin per day because one single shot of penicillin only lasts a short period of time, but the lack of human resources prevented some of the wounded soldiers from receiving the dose of penicillin that they needed[1]. To reduce the need for human labor in penicillin intake, Romansky discovered that mixing penicillin with lipids would prolong the time in which penicillin has effect. This innovation saved a lot of people from infection at the time. Lipid-based drug carriers have been developed and innovated even more throughout the years.A few years ago, the COVID-19 pandemic has facilitated advancements in vaccination technologies, including the use authorization of mRNA vaccines encapsulated in lipid nanoparticles. Traditional drug delivery methods, such as oral intake, injection, and transdermal applications, usually face challenges like low accuracy, toxicity, and variable effectiveness. However, liposomes, discovered in the 1960s, emerged as a drug carrier that, due to their specific structure, allowed for prolonged and site-specific drug release. Liposomes can encapsulate drugs of different molecular qualities, allowing lipid-based drug carriers to have excellent performance in carrying both hydrophobic and hydrophilic drugs. This paper examines the composition of liposomes, the different factors of the lipid bilayers, and the release kinetics in drug delivery. Using a hybrid modeling approach of first-order kinetics and the Higuchi model, the study simulates drug release profiles. The liposomal formulation of drugs demonstrates the potential of lipid-based delivery systems in enhancing the efficacy while minimizing side effects of treatments.

Nanoformulation of Spirooxindole and Methods for Treating Hepatocellular Carcinoma.

Objectives: This in vivo study introduces a newly developed spirooxindole derivative that is deemed safe and effective as a potential targeted therapy for various cancers. Methods: Extensive in vivo investigations, including histopathology, immunohistochemistry, and molecular biology, validated its potential for further preclinical and clinical exploration, necessitating comprehensive examinations of its bioavailability, pharmacodynamics, and pharmacokinetics. Additionally, this study involves the development of a commercially viable proniosomal drug delivery system for the compound, facilitating controlled drug release. Results: The data revealed efficacy of spirooxindole derivative in halting the progression of liver cancer, metastasis, and portal vein thrombosis, with potential implications for enhancing regeneration and recovery of early-stage cancer cells in multiple organs, thereby improving recovery rates and remission among cancer patients. The proniosomes, loaded with the compound, exhibited high entrapment efficiency and prolonged drug release rates of up to 12 h in vitro. The optimized formula demonstrated superior drug release percentages and stability compared to conventional niosomes. Further analysis via FTIR and DSC confirmed the absence of chemical interactions and proper entrapment of the compound within the nanovesicles, indicating a stable and effective drug delivery system. Conclusions: This study presents a novel, safe, and effective chemical entity of spirooxindole derivatives for further preclinical and clinical studies.

Enhancing transdermal drug delivery: formulation and evaluation of simvastatin-loaded invasomes in carbopol gel for improved permeability and prolonged release

Abstract The transdermal pathway serves as a significant route for achieving localized or systemic effects. Within this context, the stratum corneum is a crucial barrier limiting the permeation of many drugs. To surmount this barrier, carriers, and nanocarriers have been utilised, notably ‘invasome’ being one such example. In our study, we formulated invasomes loaded with simvastatin using the conventional thin-layer evaporation technique. This formulation involved the use of soy phosphatidylcholine, terpene (Limonene), chloroform, and ethanol. Simvastatin-loadedinvasomes were incorporated into a carbopol 934 solution to create a gel. We prepared and assessed different formulationsfor various parameters, including zeta potential, scanning electron microscopy, entrapment efficiency, viscosity, and drug content, and conducted in vitro studies. The entrapment efficiency was as high as 83.17±0.61%. The maximum in vitro drug permeation (45.44±0.4%) was found in the gel with 0.5% soy phosphatidylcholine and 0.25% terpene. Upon evaluating these parameters, our findings suggest that the simvastatin invasomal gel effectively enhances drug permeability across membranes and successfully achieves prolonged drug release.

Overcoming drug delivery challenges with lipid-based nanofibers for enhanced wound repair.

Wound healing is a dynamic, multi-phase process that includes haemostasis, tissue regeneration, cellular proliferation, and matrix modification. Traditional wound care procedures frequently encounter complications such as delayed healing and infection, demanding new therapeutic approaches. In this context, nanomaterial-based devices provide considerable benefits due to their capacity to improve medication delivery and tissue healing. We suggest a lipid-based nanofiber formulation for wound treatment that overcomes the restricted skin penetration of hydrophilic niacin, a strong wound healing agent. Niacin-loaded nanofibers (NLNFs) were manufactured utilizing glyceryl monostearate (GMS) by a self-assembly process, which included high-pressure homogenization and probe sonication for optimum nanostructure creation. The NLNFs were physicochemically characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, scanning electron microscopy (SEM) and surface profilometry to determine their morphology and homogeneity, and a drop shape analyser was used to determine hydrophobicity. In vitro tests revealed prolonged drug release, great cytocompatibility, and strong antioxidant activity, indicating superior free radical scavenging capacity. Ex vivo tests, such as the Draize skin irritation test, skin permeation test, and drug retention assays, revealed low skin irritation, increased permeability, and efficient drug retention in skin layers. In vivo experiments showed rapid wound closure and positive histological results, which were backed by hemocompatibility tests such as hemolysis and whole blood clot analysis, validating the formulation's safety. ELISA results indicated that the NLNF-treated group had higher levels of critical wound-healing indicators than the controls. Overall, our findings suggest that NLNFs have tremendous potential as a unique and effective treatment alternative for controlling and improving wound healing processes.

γ-Cyclodextrin hydrogel for the sustained release of josamycin for potential ocular application

Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current clinical practice, application of the drug, Mitomycin C, prevents or delays fibrosis, but can lead to additional side effects, such as bleb leakage and hypotony. Previous in silico drug screening and in vitro testing has identified the known antibiotic, josamycin, as a possible alternative antifibrotic medication with potentially fewer side effects. However, a suitable ocular delivery mechanism for the hydrophobic drug to the surgical site does not yet exist. Therefore, the focus of this paper is the development of an implantable drug delivery system for sustained delivery of josamycin after glaucoma surgery based on crosslinked γ-cyclodextrin. γ-Cyclodextrin is a commonly used solubilizer which was shown to complex with josamycin, drastically increasing the drug’s solubility in aqueous solutions. A simple γ-cyclodextrin crosslinking method produced biocompatible hydrogels well-suited for implantation. The crosslinked γ − cyclodextrin retained the ability to form complexes with josamycin, resulting in a 4-fold higher drug loading efficiency when compared to linear dextran hydrogels, and prolonged drug release over 4 days.

Biomedical Application of Bovine Type I Collagen and Its Fabricated Scaffolds: A Review

The transformation of waste into wealth remains a challenging yet essential endeavor, offering opportunities for efficient solid waste management. Type I collagen, abundant in bovine tendons, serves as a valuable feedstock for the extraction of this biomaterial. Derived from slaughterhouse solid waste, bovine type I collagen acts as a foundational biomaterial for tissue engineering and regenerative medicine. This fibrous protein-based eco-material features customizable properties, including biodegradability, mechanical resilience, and surface modifiability, making it a promising alternative to synthetic and biodegradable polymers. The design and development of bioactive scaffolds remain a significant challenge in regenerative medicine, tissue engineering, and drug delivery. Collagen-based biomaterial scaffolds, which mimic the extracellular matrix, are extensively utilized as templates for tissue regeneration in biomedical applications. These scaffolds enhance wound healing and facilitate the maturation of collagen fibers, promoting the rapid formation of mature, aligned tissue at wound sites. This review provides a comprehensive analysis of the biomedical applications of collagen-based biomaterials, including their isolation and purification from bovine tendons, characterization, scaffold fabrication, ciprofloxacin/Triphala conjugation into scaffolds, biochemical and histological wound healing investigations, drug delivery, and cell culture applications. Recent advancements in chemically modified collagen and collagen-biodegradable polymer composites with controlled drug delivery for wound treatment, as well as collagen-based diffusion membranes for prolonged drug release, are also discussed.

Design and Development of Saxagliptin Microparticles for Diabetes

This study investigates the design, development, and evaluation of sustained-release Saxagliptin microparticles, utilizing Eudragit L-100 and Eudragit S-100 as polymers to achieve prolonged drug release. A total of eight formulations were prepared, employing varying drug-to-polymer ratios (1:1, 1:2, 1:3, and 1:4) for both core and coat materials. This approach facilitated an assessment of the concentration of coating material influenced the drug release rate. The solvent evaporation method proved effective in producing discrete, spherical microparticles characterized by good flowability and minimal stickiness. The surfactant Span 80 was optimized at a concentration of 1.0% to ensure optimal emulsion stability and microparticle formation. Results demonstrated that Eudragit S-100 based microparticles exhibited a significantly slower drug release profile compared to those formulated with Eudragit L-100. Notably, the formulation with a 1:4 Saxagliptin-to-Eudragit S-100 ratio achieved sustained release for up to 12 hours, confirming the trend of decreasing release rates with increasing concentrations of coating material. Dissolution data analysis revealed that the release kinetics best fit a zero-order model, indicating a constant drug release rate over time. Furthermore, the Peppas model provided the most suitable framework for understanding the drug release mechanism. The exponential coefficient (n) values indicated a non-Fickian release pattern, signifying a complex interplay between diffusion and erosion processes, which are critical for maintaining the sustained-release profile. Additionally, FTIR spectroscopy was employed to assess the compatibility of Saxagliptin within the optimized formulation. The results confirmed that the drug retained its chemical identity, with no evidence of chemical interactions between Saxagliptin and the excipients. This comprehensive study underscores the potential of Eudragit S-100 as an effective polymer for developing sustained-release formulations of Saxagliptin, enhancing patient compliance and therapeutic outcomes.

Deciphering the Antimicrobial and Antibiofilm Efficiency of Thyme Essential Oil Encapsulated Zeolitic Imidazole Framework-8 Against Foodborne Pathogens.

Food Packaging using antibacterial substances plays a vital role in food industry in controlling contamination caused by food borne pathogens. Stability and pH dependent degradation characteristics of zeolitic imidazole framework-8 (ZIF-8) makes its suitable candidate for biomedical applications. The present study focuses on thyme essential oil (TEO) encapsulated in ZIF-8 to achieve a synergistic antibacterial effect and prolonged drug release, aiming to extend the shelf life of food products. Optical, structural and surface characterizations of TEO encapsulated within ZIF-8 (ZIF-8@TEO) reveals successful incorporation of TEO into ZIF-8 nanoparticles. High drug loading and pH dependent release rate with higher release rate at acidic condition (75%) makes ZIF-8 a promising drug delivery system. ZIF-8@TEO exhibited potent antimicrobial against Staphylococcus aureus, Bacillus subtilius and Pseudomonas aeruginosa, also attenuated the biofilm forming ability of these food borne pathogens. In vitro and in vivo toxicity studies reveal the non-hemolytic and non-toxic nature indicating its biocompatible nature. The results of the study reveal that ZIF-8@TEO nanoconjugate can be used for the development of novel antibacterial nanocomposite-based films for food packaging applications.

Nanotechnology-Enhanced Controlled Release Systems in Topical Therapeutics

Topical and transdermal drug delivery are alternative routes for medications facing challenges like solubility, stability, and first-pass metabolism. However, conventional immediate-release dosage forms delivered topically have drawbacks, including poor penetration and high side ef-fects. Controlled-release nanoparticles offer a promising solution, improving drug permeation and providing controlled release. This review examines recent advances, challenges, and pro-spects of controlled-release nanoparticles for topical drug delivery. Various types of nanoparti-cles, including lipid nanoparticles, Nanoemulsions, nanoemulgels, cubosome liposomes, poly-meric nanoparticles, solid-lipid nanoparticles, lipid-polymer hybrid nanoparticles, and nanostructured lipid carriers, carbon nanotubes, nanocomposites, and protein nanoparticles have been explored for their ability to encapsulate drugs, prolong drug release, and enhance skin permeation as well as improve therapeutic outcomes. Studies have demonstrated the effective-ness of these nanoparticles in improving sustained and controlled-release topical delivery of a wide range of drugs, including poorly soluble, low degree of skin penetration, low stability, and drugs with low bioavailability and biological products. Despite their potential benefits, challeng-es such as scalability, reproducibility, and safety concerns remain. Future research should ad-dress these challenges and explore novel strategies to improve efficacy and safety by converging with microneedles and 3D nanoparticles. Ultimately, controlled-release nanoparticles have the potential to revolutionize dermatological and transdermal drug delivery, leading to improved therapeutic outcomes and patient care.

Alginate Microbeads Technology for Pharmaceutical Applications

Nowadays, microbeads are inevitable in pharmaceutical formulations with remarkable drug delivery and therapeutic outcome benefits. Usually made from biocompatible polymers, these tiny spherical particles allow for controlled and targeted delivery of APIs within the human body. Other benefits associated with microbeads include their ability to control drug release kinetics in terms of sustained or pulsatile release profiles in order to facilitate patient compliance and minimize adverse effects. This also has a minimal size and allows for adaptation for precise dosing and targeting the right sites, which augments therapeutic efficacy while cutting down systemic exposure. The need for safe and effective drug delivery systems has been a crucial aspect in the advancement of new pharmaceutical formulations. Researchers continue to seek new ways in prolonging drug release, minimizing drug wastage, and reducing the side effects of drugs. However, synthetic polymers are costly, non-biocompatible, and potentially toxic. On the other hand, sodium alginate, a natural polymer, is generally used as a matrix material because of biodegradability, low price, simplicity, and excellent biocompatibility. Sodium alginate is nontoxic when delivered orally and gives protection on the mucous membrane of the upper gastrointestinal tract. Sodium alginate is an anionic polysaccharide of natural origin wherein gelation can be obtained with the use of calcium ions to form stable microbeads. There are multiple techniques used to prepare alginate microbeads, that is, ionotropic gelation, cross-linking, emulsion gelation, spray drying, and both simple and complex coacervation phase separation methods. This review shall highlight the preparation and characterization of alginate microbeads, their therapeutic applications, and their position in the realm of controlled and novel drug delivery systems

Sustained Drug Release from Dual-Responsive Hydrogels for Local Cancer Chemo-Photothermal Therapy.

As an exceptional carrier for localized drug delivery to tumors, hydrogels can achieve prolonged drug release through careful design and adjustments, effectively targeting cancer cells and minimizing side effects. This study investigates a novel dual-responsive hydrogel system designed for the delivery of nanomedicines, focusing on drug release and the local antitumor efficacy of SN-38-cholesterol nanoparticles (SN-38-chol NPs) and polydopamine NPs (PDA NPs)/poly(n-isopropylacrylamide) (pNIPAM) hydrogels. By combining the thermosensitive properties of pNIPAM with the near-infrared (NIR) responsiveness of PDA NPs, the hydrogel aims to enhance on-demand drug release. SN-38-chol NPs, known for their stability and small size, are incorporated into the hydrogel to improve drug release dynamics. The investigation reveals a drug release cycle of over three weeks, maintaining sensitivity to both temperature and NIR light for controlled drug release. In vivo studies demonstrate the high tumor growth inhibition performance of the system after photothermal treatment induced by 808nm NIR light. These results suggest that the drug-carrying hydrogel system holds promise for diverse applications in chemical and physical therapies, including the treatment of malignant wounds, post-surgery wound healing, and direct tumor treatment. This study establishes the potential of SN-38-chol NPs and PDA NPs/pNIPAM hydrogels as effective platforms for chemo-phototherapy.

Formulation and Evaluation of Gastroretentive Floating Microspheres of Amiloride Hydrochloride

Background: Amiloride, a potassium-sparing diuretic, is widely prescribed for the management of hypertension, congestive heart failure, and various renal disorders. However, its low oral bioavailability due to extensive first-pass metabolism and short half-life necessitates frequent dosing, leading to patient inconvenience and compromised therapeutic outcomes. To address these limitations, the development of novel drug delivery systems capable of enhanced gastrointestinal retention of amiloride has garnered significant attention. Among these, gastroretentive microspheres represent a promising approach, offering prolonged drug release and improved absorption. Objectives: The present work by formulation and evaluation of gastroretentive floating microsphere (FM) plays a highly significant role as a particulate drug delivery method. Particle sizes for microspheres range from 0.1 to 200 μm, and they can be administered orally, parenterally, nasally, ophthalmologically, transdermal, colonically, etc. Site-specific targeting and enhanced release kinetics are just two of the issues that have been solved through recent advances in microspheres, including those that are mucoadhesive, hollow, floating, micro-balloons, and magnetic. Microspheres will play a key role in novel drug delivery in the future by fusing different new methods, particularly sick cell sorting, genetic materials, safe, targeted, and effective drug delivery. Discussion: Hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone, and ethylcellulose were used in varying concentrations to give the FMs of amiloride HCl release-controlling properties by increasing their bioavailability. Lactose was used as a diluent and sodium bicarbonate served as an effervescent agent. Using a solvent evaporation method approach, the gastroretentive FM of amiloride HCl was created. The generated microsphere indicated good floating strength and remained buoyant in the sustained released medium for 24 h. For systemic delivery of amiloride, a potassium-sparing diuretic and antihypertensive medication, through the oral route, a gastroretentive FMs drug delivery system was developed. The different ratios of ethylcellulose and HPMC K-100, sodium lauryl sulfate, sodium bicarbonate, and ethanol are used in formulation. The weight, thickness, percentage of moisture absorbed and lost, surface pH, folding resistance, content homogeneity, in vitro residence time, in vitro release, and ex vivo penetration of the microspheres were all assessed. Conclusion: The formulation and evaluation of gastroretentive FMs represent a significant advancement in particulate drug delivery systems. These microspheres, with particle sizes ranging from 0.1 to 200 μm, offer versatility in administration.

OPTIMIZATION OF PROCESS PARAMETERS FOR ENHANCING THE SKIN PERMEATION EFFICIENCY OF NISOLDIPINE LOADED ULTRA DEFORMABLE VESICLES IN TRANSDERMAL PATCHES

Objective: The study aimed to address the limitations of oral delivery and enhance the bioavailability of nisoldipine (NSD) through the development of transferosomal transdermal patches containing ultra-deformable transferosomes. Methods: NSD, known for its low oral bioavailability and adverse effects, was encapsulated in transferosomes using a thin film hydration method. 17 formulations were made using Box Behnken Design, varying Dipalmitoylphosphatidylcholine (DPPC), span-80, and stirring speed, and were evaluated for vesicle size, Polydispersity Index (PDI), and Entrapment Efficiency (EE%). The optimal formulation, selected based on these parameters, was combined into Transdermal Patches (TPs). The patches underwent extensive testing for physicochemical properties, in vitro and ex-vivo permeation, and skin irritancy. Results: The results showed transferosomes with Vesicle Sizes (VS) ranging from 124±2.25 to 400±1.55 nm and EE% from 52.88±0.23 to 90.01±1.58%, with Zeta Potentials (ZP) between-48 to-20 mV. The patch thickness (0.66±0.02 mm) and weight per square inch (382.1±1.69 mg) showed consistent manufacturing, while the Water Vapor Transmission Rate (WVT) (1.54±0.01g/m²/24h), low moisture content (1.07±0.01%), and regulated moisture absorption (3.78±0.01%) maintained formulation stability. In vitro and ex-vivo permeation indicated superior drug permeation for transferosomal patches (NP) compared to plain nisoldipine patches (NP-N), with permeation directly proportional to PEG-400 concentration. Additionally, the transferosomal patches were found to be free from skin irritation. Conclusion: The optimized Niosoldipine transferosomal patch (NP-3) composition displays good folding endurance (FE) 97.67±0.47, required for transdermal systems, and successfully allows drug permeation (DP) at 86.39±2.64% in a short timescale. Hence, the study concludes that transferosomal patches of NSD offer a promising approach for effective transdermal delivery, potentially improving hypertension management by providing a controlled and prolonged drug release.

FORMULATION, CHARACTERIZATION AND OPTIMIZATION OF PLGA-CHITOSAN-LOADED FATTY ACID SCAFFOLDS FOR THE TREATMENT OF DIABETIC WOUNDS

Objective: The objective of the current research to formulate Eicosapentanoic Acid/Decosahexanoic Acid (EPA/DHA)incorporated into Chitosan (CS)and Poly-Lactic-Glycolic Acid (PLGA), nanoparticles composite scaffolds to the accelerated diabetic wound healing. The main focus of this present research is to evaluate and develop the chitosan–PLGA biodegradable polymer scaffolds loaded with long-chain omega-3 Polyunsaturated Fatty Acids (PUFA’s) (EPA/DHA). Methods: Nano scaffolds were prepared by solvent evaporation method loaded with CS-PLGA, EPA and DHA to treat diabetic wounds at targeted site as pharmacotherapeutically. Upon investigation, the developed biodegradable crosslinked scaffold possesses matrix degradation, optimal porosity, prolonged drug release action than the non-cross linked scaffold. The prepared formulation containing CS-PLGA loaded with EPA/DHA were formulated as nanoscaffold for wound topical applications was carried out by using freeze drying process. Results: The prepared CS-PLGA nano scaffolds were optimized and evaluated for physicochemical properties, dynamic light scattering with a particle size of 248 nm and zeta of-24mVand Scanning Electron Microscopy (SEM) were found to be spherical. In addition, the optical properties of EPA/DHA and PLGA, along with CS, can be compared by examining their absorption and wavelength (nm) using UV-visible spectroscopy. The structural and functional groups of the prepared end products were characterized by Fourier-Transformed Infrared Spectroscopy (FT-IR) has shown good compatibility with excipients and nanoformulaton, in vitro drug release studies done by using dialysis bag membrane results find that first-order Higuchi model was followed showing 20% release in first 0.2 h. MTT(3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide) assay was carried out and it showed that both crosslinked and non-crosslinked scaffolds(110 and 120%) improved cell growth when compared to control (100%). Conclusion: Finally, the results showed that the PLGA, CS nanoscaffolds containing 98% of PUFA’s (EPA/DHA) have increased in proinflammatory cytokines production at the particular wound site and thus accelerated healing activity, depending on the pre-clinical studies have trespassed, the therapeutic potential to penetrating at wound site. The optimized nanoformulation could be a better formulation for targeting and treatment of diabetic wounds at an optimal ratio.