Sustained Drug Release Research Articles

Nanostructured Lipid Carrier-Mediated Transdermal Delivery System of Glibenclamide for Gestational Diabetes: Pharmacokinetic and Pharmacodynamic Evaluation.

Gestational diabetes mellitus (GDM) poses significant risks during pregnancy for both mother and fetus. Adherence to oral antidiabetic medications, like glibenclamide (GB), can be challenging, necessitating novel drug delivery methods. Nanostructured lipid carriers (NLC) offer a promising approach by efficiently permeating the skin due to their small size and lipid-based composition. This study aimed to develop and evaluate transdermal patches loaded with glibenclamide NLCs to treat GDM. Glibenclamide NLCs were prepared using hot homogenization with ultrasonication and melt dispersion method. A central composite design was utilized to optimize the formulations. Transdermal patches containing optimized NLCs were developed using HPMC K 100 and Eudragit L polymers. The patches were evaluated for various parameters, and their pharmacokinetic and pharmacodynamic studies were carried out to assess their safety and efficacy. Optimized NLCs efficiently permeated rat skin. Cell viability studies indicated the nontoxicity of the formulations. NLC-loaded transdermal patches (F2 and F7) showed drug release of 1098 μg/cm2 and 1001.83 μg/cm2 in 24 h, with a 2.5-fold higher flux and permeation coefficient than the GB patch. Pharmacokinetic analysis revealed Tmax of 8 and 10 h and Cmax of 7127 ng/ml and 7960 ng/ml for F2 and F7, respectively, ensuring sustained drug action. AUC0-α was 625681 ng/ml·h and 363625 ng/ml·h for F2 and F7, respectively, indicating improved bioavailability. Transdermal patches incorporating NLCs hold promise for enhancing glibenclamide's therapeutic efficacy in GDM treatment. Improved skin permeation, sustained drug release, and enhanced bioavailability make NLC-based transdermal patches a potential alternative with better patient compliance.

Cubosomes hydrogel containing silver based organometallic compounds for enhanced wound healing of burns: In vitro and in vivo studies

The aim of this study is to investigate the treatment of burn wounds and bacterial infections, specifically focusing on silver(I) N-heterocyclic carbene (Ag-NHC) loaded into cubosomes. Ag-NHC is an organometallic complex of silver (Ag) and can be considered an active pharmaceutical ingredient for the topical treatment of burns. A novel nanoparticle system, cubosome dispersions, was formulated using high pressure homogenization methods with different concentrations of lipid phase glyceryl monooleate (GMO), surfactants such as poloxamer 407 (F-127), and polyvinyl alcohol (PVA). The optimized formulation (U6) was characterized by in vitro drug release profile (90.54 ± 1.17 %), particle size (126.7 ± 0.98 nm), zeta potential (−21.6 ± 6.83 mV), entrapment efficiency (89.30 ± 1.46 %), and morphology as observed by transmission electron microscopy (TEM). The U6 formulation was incorporated into a hydrogel containing Carbopol 940 to form a cubosomal hydrogel (cubogel). The cubogel was characterized by the in vitro release of Ag-NHC (92 %), entrapment efficiency (>90 %), pH (5.3), viscosity (1.2 cP), spreadability, and TEM. From the in vitro drug release pattern, it was concluded that the U6 formulation showed slow and sustained drug release over 24 h, and demonstrated superior burn healing compared to marketed products. The in vivo wound healing study revealed that the cubogel demonstrated a superior burn healing rate compared to commercially available products (Quench® and Clotrimazole®). The in vivo histopathological results showed that the prepared cubogel was effective in treating second-degree burns, with no side effects or skin irritation, compared to commercial products. Additionally, Ag-NHC-loaded cubogel facilitated sustained release for treating burn wounds without any bacterial infections. The current findings provide a strong basis for the initiating phase 0 clinal trials, highlighting significant potential for the further research to benefit the pharmaceutical industry.

Preparation of a thermosensitive and antibacterial in situ gel using poloxamer-quaternized chitosan for sustained ocular delivery of Levofloxacin hydrochloride

In this study, a thermosensitive in situ gel with porous structure was developed using poloxamer (Po) and N-(2-hydroxy-3-trimethyl ammonium) propyl chitosan chloride (HTCC). The poloxamer-quaternized chitosan (Po-HTCC) in situ gel exhibited superior rheological property, water absorption capacity and antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pyogenes, making it well-suited for ocular applications. Scanning electron microscope revealed a macroporous architecture with pore sizes ranging from 1 to 2 μm, suggesting that the gel has desirable breathability, corneal adhesion capability, and overall conformability. In vitro drug release assay was conducted with levofloxacin hydrochloride, demonstrating that sustained release over 48 h could be achieved at 34 °C, with approximately 80 % of the drug released within this timeframe. Computational simulations revealed substantial binding affinity between the material and the Escherichia coli outer membrane lipopolysaccharide-associated protein and corneal mucin. The protein showing the strongest binding energy to N-(2-hydroxy-3-trimethyl ammonium) propyl chitosan chloride (HTCC), as calculated by the Molecular Mechanics Generalized Born Surface Area Method (MM-GBSA), was LptD-LptE, with a binding energy of −61.14 ± 4.72 kcal/mol. These results underscore the potential of this system for effective and convenient ocular delivery with sustained drug release.

Silicone-based AC102-loaded cochlear implant coatings protect residual hearing in an animal model of cochlear implantation

Cochlear implant users with residual hearing benefit synergistically from combined electrical stimulation via the cochlear implant and preserved residual hearing after surgery. However, direct mechanical trauma and subsequent inflammation may deteriorate hearing function. AC102, a novel otoprotective pyridoindole with anti-apoptotic and anti-oxidative properties significantly improved hearing recovery following cochlear implantation when administered intratympanically prior to surgery. Additionally, AC102 exerts neurotrophic effects, possibly aiding in the preservation of auditory nerve fibers and spiral ganglion neurons. Rapid clearance of the drug, however, might be a limiting factor to further attenuate the inflammatory response and maintain neuronal health. The aim of the current study was to design an AC102-loaded electrode array for sustained drug delivery and investigate its effects in hearing preservation cochlear implantation.First, the release-kinetics of AC102 were investigated in vitro and modelled by the Higuchi equation of drug release. An electrode array coated with 10% AC102 was manufactured, its release kinetics evaluated, and subsequently tested in vivo. 20 normal hearing Mongolian gerbils were unilaterally implanted with an AC102-loaded or an unloaded control electrode. Compound action potentials were measured prior to cochlear implantation and serially over 28 days. Hair cells, inner hair cell synapses, and auditory nerve fibers were quantified in cochlear whole-mounts by immunofluorescence staining.AC102 release from silicone coating could be predictably modelled by the Higuchi equation of drug release. The electrode array with an AC102-silicone depot enabled non-linear sustained drug release with initially higher release concentrations. In vivo, the AC102-loaded electrode array significantly recovered auditory threshold shifts near the maximum insertion depth over 28 days. In the apical region, a significant recovery was noticed only until day 14, after which threshold shifts aligned between groups. Histologically, AC102-loaded electrodes significantly preserved outer hair cells apical of the maximum insertion depth and inner hair cells and neuronal structures at the tip of the inserted electrode.In conclusion, the drug-loaded electrode arrays could predictably release AC102 over a period of 28 days. AC102 enabled the restoration of auditory thresholds near the area of maximum insertion, which is the desired region to be preserved in cochlear implant recipients with residual hearing.

Multi-layered tablets: A comprehensive review on technologies and research

Multilayered tablets combine two or more active pharmaceutical ingredients for an improved therapeutic effect or to achieve a specific drug release profile. In multi-layered tablets two or more active pharmaceutical ingredients can be combined where one layer or one drug may be for immediate release and the other layer of the drug may be for sustained release of drug i.e., one layer is a loading dose and the other layer may be a maintenance dose. Multilayered tablets can help overcome the drug interactions and the disadvantages of non-linearity associated with diffusion-controlled matrix devices, providing an increased surface area and increasing drug release rate with time. This review article discusses different techniques involved in the preparation of multi-layered tablets along with research on multi-layered tablets.

L-Cystine-Based Polyurethane as a Drug-Delivery Vehicle in Targeted Cancer Therapy and Biomedical Applications.

Controlled and sustained drug release is a critical aspect of drug-delivery systems (DDSs) that can be used in chemotherapy while ensuring therapy effectiveness and biosafety. Hence, polyurethane (PU) is modified using a biomolecule Cystine (CYS) for protracted drug release, aiming to enhance cancer treatment efficacy while minimizing adverse side effects in tumor patients. To confirm the formation of a polymer structure, characterization techniques such as NMR and FTIR are used, and the morphology is determined using SEM. Biocompatibility of the synthesized polymers is evaluated through cellular assessments, including MTT assay, cell adhesion, and antibacterial assay along with drug release using an anticancer drug, Paclitaxel (PTX). Notably, the incorporation of PTX in the polymer matrix results in minimal mortality (85% viable cells) rates in healthy cells (3T3), in contrast to a 56% mortality rate observed with the pure drug. While PTX shows a burst release and kills cancer cells only for the first 24 h, PU loaded with the drug shows sustained release and kills the cancer cells for 3 days. This vehicle selectively kills 59% of SiHA cells after a consecutive study of 3 days, which highlights the potential of this newly designed vehicle for effective drug delivery, particularly in anticancer treatments. Moreover, cystine's antibacterial property adds up with PU; hence, PU shows antibacterial activity against Staphylococcus aureus (MIC, 20 μg/mL) and also acts as a reductive oxygen species scavenger. Therefore, modifying PU with CYS has shown sustained release of PTX along with a selective effect on cells, underscoring its significance as a superior delivery agent and supported by a shred of convincing evidence.

3D-printing of dipyridamole/thermoplastic polyurethane materials for bone regeneration.

Tissue engineering combines biology and engineering to develop constructs for repairing or replacing damaged tissues. Over the last few years, this field has seen significant advancements, particularly in bone tissue engineering. 3D printing has revolutionised this field, allowing the fabrication of patient- or defect-specific scaffolds to enhance bone regeneration, thus providing a personalised approach that offers unique control over the shape, size, and structure of 3D-printed constructs. Accordingly, thermoplastic polyurethane (TPU)-based 3D-printed scaffolds loaded with dipyridamole (DIP) were manufactured to evaluate their in vitro osteogenic capacity. The fabricated DIP-loaded TPU-based scaffolds were fully characterised, and their physical and mechanical properties analysed. Moreover, the DIP release profile, the biocompatibility of scaffolds with murine calvaria-derived pre-osteoblastic cells, and the intracellular alkaline phosphatase (ALP) assay to verify osteogenic ability were evaluated. The results suggested that these materials offered an attractive option for preparing bone scaffolds due to their mechanical properties. Indeed, the addition of DIP in concentrations up to 10% did not influence the compression modulus. Moreover, DIP-loaded scaffolds containing the highest DIP cargo (10% w/w) were able to provide sustained drug release for up to 30 days. Furthermore, cell viability, proliferation, and osteogenesis of MC3T3-E1 cells were significantly increased with the highest DIP cargo (10% w/w) compared to the control samples. These promising results suggest that DIP-loaded TPU-based scaffolds may enhance bone regeneration. Combined with the flexibility of 3D printing, this approach has the potential to enable the creation of customized scaffolds tailored to patients' needs at the point of care in the future.

Thymoquinone loaded nanoemulgel in streptozotocin induced diabetic wound.

Aim: To treat diabetic wound healing with a novel Thymoquinone (TQ) loaded nanoformulation by using combination of essentials oils.Methods: TQ nanoemulsion (NE) was developed with seabuckthorn & lavender essential oils by phase inversion method and mixture design. Further, DIAGEL is obtained by incorporating NE into 1% carbopol®934. Furthermore, particle size, polydispersity index, thermodynamic stability studies, rheology, spreadability, drug content, in-vitro drug release, ex-vivo permeation, anti-oxidant assay, antimicrobial studies, angioirritance, HAT-CAM assay, in-vitro and in-vivo studies were determined.Results: NE has a particle size of 17.79±0.61nm, 0.206±0.012 PDI & found to be thermodynamically stable. DIAGEL exhibited pseudoplastic behavior, sustained drug release, better permeation of TQ and a drug content of 98.54±0.08%. DIAGEL stored for 6months at room temperature and 2-8°C showed no degradation. Further, an improved angiogenesis, absence of angio-irritancy, remarkable antioxidant and antimicrobial activities against Candida albicans & S. aureus were observed. Cytotoxicity analysis revealed nearly 2.28 -folds higherIC50 value than drug solution. Furthermore, inflammatory mediators were reduced in DIAGEL treated animal groups. The histopathological studies confirmed skin healing with regeneration and granulation of tissue.Conclusion: The novel formulation has strong anti-inflammatory, angiogenesis, antioxidant and appreciable diabetic wound healing properties.

Single-Component Starch-Based Hydrogels for Therapeutic Delivery.

Hydrogels are interesting materials as delivery systems of various therapeutic agents, mainly due to the water-swollen network and the localized and sustained drug release. Herein, single-component starch-based hydrogels with enhanced degradation rates were produced by applying a facile synthesis and proposed for a novel delivery system of therapeutic molecules. Starch was oxidized with sodium periodate in water and mild conditions to generate aldehyde derivatives that, after a freeze-thaw procedure, were allowed to compact and stable hydrogels. Oxidized starch was also cross-linked with asparagine through a Schiff base reaction to link the active molecule directly to the polysaccharide structure. The materials were structurally and morphologically characterized, and the ability to adsorb and release over time an active molecule was proven by qNMR spectroscopy. The cytotoxicity was evaluated on CAL-27 cell line (oral squamous cell carcinoma). Results indicated that synthesized hydrogels lead to a "frozen proliferative" state on cells due to the swelling capability in the cell medium. This behavior was confirmed by flow cytometry data indicating the hydrogels induced less "early apoptosis" and more "late apoptosis" in the cells, compared to the untreated control. Since the proposed materials are able to control the cell proliferation, they could open a new scenario within the field of precise therapeutic applications.

Poly(Vinyl Alcohol) Drug and PVA-Drug-Surfactant Complex Organogel with Dimethyl Sulfoxide as a Drug Delivery System.

The relevance of active research lies in the need to develop new technologies to improve drug delivery methods for the effective treatment of wound healing. Additionally, the potential application of organogels in other areas of biomedicine, such as creating medical patches with controlled drug delivery, indicates a wide range of possibilities for using this technology. This study focuses on developing controlled drug delivery systems using organogels as carriers for ceftriaxone and ofloxacin. By selecting optimal formulations, organogels were created to immobilize the drugs, facilitating their effective and sustained release. The swelling behavior of the hydrogels was studied, showing a swelling coefficient between 16 and 32%, indicating their ability to absorb liquid relative to their weight. Drug release studies demonstrated that ceftriaxone was released 1.8 times slower than ofloxacin, ensuring a more controlled delivery. Microbiological tests confirmed that the organogels containing ofloxacin exhibited antimicrobial activity against Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. However, it was a challenge to estimate activity for the model antibiotic ceftriaxone due to bacterial resistance to it. Organogel poly(vinyl alcohol) (PVA)-DMSO-alginate modifications with surfactant cetylpyridinium bromide led to the formation of a polyelectrolyte complex on the interphase, allowing further enhanced the prolonged release of the drugs. The research identified that the optimal compositions for sustained drug release were organogels with compositions PVA (10%)-PVP (1%) DMSO (50%) and PVA (10%)-DMSO (50%) formulations, illustrating the transparent nature of these organogels making them suitable for ophthalmological application. Various organogels compositions (PVA-DMSO, PVA-poly(vinylpyrrolidone)-DMSO, PVA-DMSO-alginate, PVA-DMSO-PLGA, PVA-DMSO-drug-surfactant) loaded with ceftriaxone, ofloxacin, and surfactant were prepared and characterized, highlighting their potential use in antibiotic patches for wound healing. These organogels illustrate promising results for localized treatment of infections in wounds, cuts, burns, and other skin lesions.

Lignin-chitosan-based biocomposite film for the localized delivery of TLR7 agonist imiquimod

Abstract Background As the leading form of non-melanoma skin cancer, basal cell carcinoma (BCC) presents a considerable challenge to healthcare systems, owing to its widespread occurrence. Current treatment options, such as surgical excision, cryotherapy, and localized therapies like imiquimod or 5-fluorouracil, face challenges, especially in designing drug delivery systems that provide prolonged therapeutic effects. This study aims to develop bio-composite polymeric films for localized drug delivery using natural polymers, lignin, and chitosan, to enhance the delivery of the TLR7 agonist imiquimod for BCC treatment. Results The optimized biofilms were prepared by adjusting the polymer ratio and drying techniques to achieve a balanced composition for localized imiquimod delivery. FTIR and DSC characterization confirmed successful drug incorporation into the biofilms, while microscopic studies revealed the biofilms homogeneity and fibrous nature. Drug release studies demonstrated pH-dependent kinetics, with higher release rates at neutral pH. The biofilms exhibited slow and sustained drug release, promising prolonged therapeutic effects. Additionally, the biofilms were non-hemolytic, showed significant antioxidant activity, and demonstrated selective cytotoxicity against B16–F10 mouse skin melanoma cells. Conclusions This study suggests that lignin-chitosan-based imiquimod-loaded biofilms hold potential as an effective topical treatment for BCC. The biofilm’s ability to provide sustained drug release, along with their biocompatibility and selective cytotoxicity, indicates a promising approach to enhancing BCC therapy. Graphical abstract

Optimization and characterization of electrospun bilayered PVA/collagen nanofibers loaded with quercetin for tissue engineering applications

Bilayered electrospun membranes for skin tissue engineering and wound dressings were developed using Poly vinyl alcohol (PVA), collagen (COLL), chitosan (CH), and a tamarind seed polysaccharide (TSP) are crosslinked with quercetin (QU). To maintain a sustained release of drug from the membrane we have developed a novel crosslinked two layered stable PVA fibrous mat, top layer composed of PVA/CH/TSP and quercetin and the bottom layer is composed of PVA/CH/COLL. Developed bilayered scaffolds were characterized using Field Emission Scanning Electron Microscope (FE-SEM) and their surface morphologies exhibited random fibrous orientation with porous morphology. Cross sectional images showed the junction of the bilayered scaffold with different fiber morphology between the layers. The results revealed fibrous bilayer separation confirming the bilayered scaffold with uniform porosity which is beneficial for tissue engineering application, moreover the PVA fibrous mats are stable after crosslinking it with quercetin, more than 24 h. Invitro biological studies results also showed desirable cell viability on fibroblast cells with increased proliferation and adhesion on the bilayer material making it potential for targeted tissue engineering application.

Tripolar Bolalipids as Key Components of Sustained-Release Drug Delivery Systems.

Controlling passive diffusion through an amphiphilic membrane is a key factor for the development of future smart generations of drug delivery systems. It also plays a crucial role in understanding fundamental biological systems through the design of new artificial cell models. We report herein a new concept of bolalipids designed as key components for the control of the membrane's permeability. Built on the scaffold of two natural phospholipids connected in the terminal fatty chain region through a polar linker, this specific bola pattern adopts two extreme conformations while self-assembling in water: a bent conformation, responsible for the curvature of the membrane, and an extended conformation, responsible for decreasing the membrane's fluidity. We also designed a bolalipid possessing an ester linker in the lipidic interface that enables stabilization of highly leaky DMPC SUV-liposomes. The nanoparticles were characterized by dynamic light scattering, cryogenic transmission electron microscopy, Fourier transform infrared, differential scanning calorimetry, fluorimetry, and coarse-grained molecular dynamics in order to validate this proof of concept.

Formulation and Evaluation of Mucoadhesive Buccal Tablets of Carvedilol

The aim of the study was to formulate and evaluate the carvedilol buccal tablets using HPMC K4M and xanthan gum as polymer. Buccal tablets of carvedilol were prepared by direct compression technique by using polymer in combination at different concentration. Drug excipient compatibility study indicates that there is no interaction between the excipient and the drug. Total seven batches were prepared and subjected to evaluation parameters. Pre-compression parameters for all batches showed excellent flow propertied of powder bled. Prepared buccal tablets were evaluated for various post compression parameters like hardness, thickness, weight variation, drug content, and friability, % swelling index, muco-adhesive strength and in vitro drug release. The harness of all batches was optimum showed good mechanical strength; thickness of tablets was uniform in all formulations the weight variation test of all the formulation was found to be within the limits of pharmacopoeial standard. % swelling index for all the batch formulation was optimum and seen to increase with increase in polymer concentration. Mucoadhesive strength was also showed acceptable results for all batch formulations which satisfy the need of mucoadhesive tablets. The in vitro dissolution profile of all the formulation showed sustained release of drug, for extended periods of time. The optimized formulation of F4 prepared with was consider as the optimized formulation with respect to drug content, % swelling index, Mucoadhesive strength and in vitro drug release pattern for 8 hrs. Formulation F4 showed highest 98.32±1.55 % drug release at the end of 8 hrs. Optimized formulation F4 was found to be stable during the stability studies for 3 month indicating good stability of the formulation. Keywords: carvedilol, Mucoadhesive strength, Optimized formulation, buccal tablets.

Formulation, Development and Evaluation of Pulsatile Tablets of Etoricoxib

Aim: This research aimed to develop a pulsatile drug delivery system (PDDS) for etoricoxib, selective COX-2 inhibitor analgesic, to address the limitations of conventional formulations by releasing the drug at specific intervals aligned with the circadian rhythm of pain. Method: Core tablets containing Etoricoxib were prepared by direct compression with varied concentrations of croscarmellose sodium as a superdisintegrant. The optimized core tablets were coated using hydrophilic (HPMC K4M) and hydrophobic (ethyl cellulose) polymers in different ratios to create press-coated pulsatile tablets with varying lag times. Physical properties hardness, thickness, friability, and disintegration, drug content uniformity, and in vitro release were evaluated. Results: The core tablets exhibited rapid drug release, with batch C3 showing 98.61% release within 60 minutes. Press-coated formulations with different polymer ratios exhibited varying lag times, with batch F3 achieving the optimal balance—providing a 4-hour lag time and 96.6% drug release over 8 hours. Stability studies confirmed the physical and chemical stability of the optimized formulation (F3) over 6 months under accelerated conditions. Conclusion: The developed press-coated pulsatile tablets of etoricoxib successfully achieved a controlled lag time and sustained drug release profile, making them suitable for chronopharmacological management of pain. Keywords: Etoricoxib, Pulsatile Drug Delivery System, Chronopharmacology, Press-Coated Tablets. etc

Timolol Maleate Microspheres: An Ingenious Carrier for Sustained Release Antihypertensive Formulation

Background: Timolol maleate is classified as a BCS Class I drug and functions as a non-selective β-adrenergic receptor blocker. Its ability to lower heart rate and cardiac output has led to its widespread use in the treatment of hypertension. Objective: Timolol maleate has a short half-life and is rapidly cleared from the body, which limits its therapeutic effectiveness, requiring frequent dosing and potentially affecting patient adherence. To overcome these challenges, sustained-release microspheres of Timolol maleate were developed using the ion gelation method. Method: The ion gelation technique was employed to create the microspheres due to its various advantages, including ease of use, scalability and gentle processing conditions. Results: All batches exhibited a comparatively lower swelling index in 0.1M HCl (pH 1.2) than in SIF (pH 6.8). It was observed that increasing the concentration of sodium alginate resulted in higher drug content. The microspheres were sized between 400 and 900 μm and demonstrated excellent flow characteristics. An optimized batch achieved an entrapment efficiency of 88.83% and released 92.15% of the drug over 7 hrs. Furthermore, stability studies conducted according to ICH Q1A(R2) for 3 months at 5±3°C and 25±2°C/60±5% RH indicated no significant changes in evaluation parameters. Conclusion: The optimized Timolol maleate-loaded microspheres effectively provided sustained drug release through the membrane over 7 hrs. This study contributes to the development of improved drug delivery systems for better hypertension management, addressing the unmet needs in patient compliance. Keywords: Timolol Maleate, Microspheres, Ion gelation method, Sodium alginate, Calcium chloride, Sustained release, Hypertension

ENHANCING TRANSDERMAL DELIVERY OF POORLY WATER-SOLUBLE NSAIDS: EFFECTIVE STRATEGIES

Transdermal drug delivery offers significant advantages for administering non-steroidal anti-inflammatory drugs (NSAIDs) and anti-complementary drugs, particularly those with poor water solubility. This delivery route bypasses first-pass metabolism and gastrointestinal degradation, enhancing bioavailability and patient compliance. However, the stratum corneum, the outermost layer of the skin, poses a formidable barrier to drug permeation. To address this challenge, several innovative strategies have been developed to improve the transdermal delivery of these poorly soluble drugs. Chemical enhancers, such as alcohols, fatty acids, and surfactants, can disrupt the lipid structure of the stratum corneum, increasing drug solubility and permeability. Nanoformulations, including liposomes, niosomes, solid lipid nanoparticles, and nanoemulsions, enhance drug solubility, provide protection against degradation, and facilitate controlled release with deeper skin penetration. Prodrugs, designed to convert into the active drug within the skin, can improve solubility and permeability. Physical methods like microneedles, iontophoresis, and phonophoresis create micropores or use electrical and ultrasound waves to enhance permeation without compromising skin integrity. Cyclodextrins form inclusion complexes with drugs, boosting solubility and stability. Hydrogels and polymer-based formulations create a moist environment for sustained drug release and better absorption. Co-solvents and surfactants, such as ethanol and DMSO, further enhance solubility and disrupt the stratum corneum to facilitate drug penetration. Electroporation and thermal ablation transiently disrupt the skin barrier, significantly improving drug permeation. These strategies, individually or in combination, hold promise for optimizing the transdermal delivery of poorly water-soluble NSAIDs and anticomplementary drugs, ensuring effective therapeutic outcomes and improved patient compliance.

Development, QbD-based optimisation, in-vivo pharmacokinetics, and ex-vivo evaluation of Eudragit® RS 100 loaded flurbiprofen nanoparticles for oral drug delivery

This study aims to develop and evaluate flurbiprofen-loaded polymeric nanoparticles to achieve sustained drug release, enhancing therapeutic efficacy and minimising dosing frequency for improved patient outcomes. Flurbiprofen-loaded polymeric nanoparticles were prepared using a tubular microreactor and spray drying, optimised via Box-Behnken Design. Characterisation included particle size, encapsulation efficiency, in vitro and in vivo drug release, and techniques like FTIR, DSC, XRD, and SEM. Statistical analysis ensured robust formulation optimisation and evaluation of performance. The optimised batch of flurbiprofen-loaded polymeric nanoparticles was characterised for mean diameter, PDI, zeta potential, drug release, and EE% were found to be 306.1 ± 6.00 nm, 0.184 ± 0.02 Mw, −23.6 ± 1.51 mV, 85.46 ± 0.53% and 92.31 ± 0.84 (% w/w) respectively. Pharmacokinetic analysis further confirmed the sustained release, extending up to 12 hours and enhancing permeation compared to the pure flurbiprofen. Sustained release of flurbiprofen-loaded polymeric nanoparticles significantly enhances therapeutic effectiveness for inflammatory conditions.

Preparation and characterization of poly(ethylene glycol)-b-poly(tert-butyl methacrylate) micelles as potential nanocarriers for donepezil

Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer’s disease drug, to enhance its transport across the blood–brain barrier (BBB). Poly(ethylene glycol)-b-poly(tert-butyl methacrylate) amphiphilic block copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated via colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an in vitro BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer’s treatment by enhancing donepezil’s delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer’s therapy.

Advances in Transdermal Drug Delivery: The Development of Microneedle Technology for Improved Therapeutic Outcomes

Transdermal Drug Delivery Systems (TDDS) represent a significant advancement in therapeutic administration by allowing drugs to bypass the gastrointestinal system and first-pass hepatic metabolism, enhancing patient compliance, and enabling sustained drug release. However, traditional TDDS face limitations, including resistance from the skin's natural barrier and limited efficacy in delivering large or hydrophilic molecules. Microneedle (MN) technology offers a breakthrough solution, using minimally invasive micron-sized needles to bypass the stratum corneum, facilitating efficient drug delivery without significant pain or discomfort. This review explores the evolution and recent advancements in microneedle technology, highlighting its role in overcoming the limitations of conventional TDDS. Microneedles have been shown to enhance drug bioavailability, reduce side effects, and expand the range of deliverable therapeutics, including vaccines, insulin, and genetic materials. The development of bioinspired 4D microneedles further extends their application to diagnostics and cosmetic treatments, positioning MNs as a versatile tool in modern medicine. Key sections of the review focus on the types of microneedles—solid, coated, dissolving, hollow, and hydrogel-forming—and their respective fabrication methods, materials, and drug delivery mechanisms. The review also discusses the challenges related to scaling up production, ensuring consistent quality, and regulatory hurdles in achieving clinical approval. Future directions include the integration of microneedles with nanotechnology, combination therapies, and sustainable design, particularly in developing regions where biodegradable materials may address environmental and disposal concerns. The potential for microneedle technology to revolutionize transdermal drug delivery, diagnostics, and therapeutic monitoring is significant, with ongoing research paving the way for multifunctional applications that can reshape patient care and treatment modalities.