Stretchable Biodegradable Elastomer Patch for Sustained Transdermal Delivery of Lidocaine

Microparticles with size less than 3 µm, able to be taken up by M cell of Peyer's patches for the drug delivery to the Gut Associated Limphoid Tissue (GALT), were developed in order to improve oral bioavailability of Polymyxin B (PMB). Less than 3 µm alginate microparticles resistant to gastro-intestinal media were prepared by spray-drying technique and cross-linking by calcium ions and chitosan. The cross-linked microparticles were evaluated for PMB content by spectrophotometric method, alginate/PMB interaction by rheological study, cross-linking degree by EDS analysis and PMB activity by microbiological assay. By modulating the polymer cross-linking degree, cationic PMB interacted on alginate chains leading to a proper PMB loading as well as antibiotic retention in gastric environment and sustained delivery in intestinal fluid. Moreover, the procedure resulted suitable for PMB biological activity preservation.

Perindopril Erbumine is a widely used angiotensin-converting enzyme (ACE) inhibitor for managing hypertension and cardiovascular diseases. Its dual action of lowering blood pressure and mitigating inflammation makes it a cornerstone treatment in these conditions. However, its oral administration often results in suboptimal bioavailability and gastrointestinal side effects. This study aimed to develop and characterize a dissolving microneedle (dMN) patch for the transdermal delivery of Perindopril Erbumine to enhance therapeutic efficacy and patient compliance. A Perindopril Erbumine-loaded microneedle patch was fabricated using chitosan and polyvinyl alcohol (PVA) using the solvent casting method. The microneedle patch was evaluated for physical properties, mechanical strength, drug loading, and moisture content. Ex-vivo permeation through rat skin and in-vivo pharmacokinetic studies in rabbits was conducted to compare its performance with a marketed oral Perindopril Erbumine formulation. The developed patch demonstrated effective skin penetration, controlled drug release, and a six-fold enhancement in cumulative drug permeation (82.45% ± 1.54) compared to the oral solution (14.32% ± 1.60). The pharmacokinetic study revealed prolonged drug release, with a 7.9-fold increase in half-life (7.739 ± 0.243h vs. 0.986 ± 0.93h) and a significantly higher area under the curve (AUC) for the microneedle patch. Skin irritation studies confirmed the biocompatibility of the formulation, with no significant adverse effects observed. These findings highlight the potential of Perindopril Erbumine-loaded dissolving microneedles as a promising transdermal delivery system for improved therapeutic outcomes in managing hypertension and inflammation-related vascular conditions, potentially reducing inflammation through enhanced and targeted drug delivery.

Methotrexate (MTX) is a first-line treatment for rheumatoid arthritis (RA), but its clinical use is greatly limited by the adverse effects and poor patient compliance caused by traditional oral administration or injection. In recent years, some transdermal drug delivery systems have received considerable attention due to overcoming these shortcomings. In this study, we developed dissolving microneedle patch (DMNP) for transdermal delivery of MTX to treat RA safely and effectively. The morphology, mechanical strength, skin insertion, drug content, in vitro transdermal delivery, and other properties of DMNP were characterized. Meanwhile, the adjuvant-induced arthritis model of rats was established to investigate the therapeutic effect of MTX-loaded DMNP in vivo. The results showed that the microneedles had excellent morphology with neat array and complete needles, good puncture performance and mechanical strength, and rapid intradermal dissolution rate. In vitro transdermal delivery results indicated that microneedles could significantly increase drug transdermal permeation compared with the cream group. The pharmacological study showed that MTX-loaded DMNP significantly alleviated paw swelling, inhibit inflammatory response via downregulating the levels of TNF-α and IL-1β, relieved synovium destruction with less cartilage erosion, and slowed the progression of RA in AIA rats. Besides, DMNP presented better therapeutic performance than cream or intragastric administration at the same dosage of MTX. In conclusion, the MTX-loaded dissolving microneedle patch has advantages of safety, convenience, and high efficacy over conventional administrations, laying a foundation for the transdermal drug delivery system treatment of rheumatoid arthritis.

Development of transethosomes patch for delivery atorvastatin calcium transdermally: In vitro and in vivo studies.

Effective myocardial regeneration following infarction remains a major clinical challenge due to the complex and dynamic pathological microenvironment. Current clinical management fails to adequately modulate the dynamic infarct microenvironment, where dysregulated inflammation and insufficient angiogenesis represent key therapeutic targets. To address this challenge, we developed a spatiotemporally coordinated microneedle (MN) patch based on curcumin-conjugated gelatin methacrylate (Cur-GelMA) hydrogel for co-delivery of curcumin and stromal cell-derived factor-1α (SDF-1α). The engineered Cur-GelMA network significantly enhanced curcumin solubility and bioavailability, while PDMS micromolding enabled fabrication of mechanically robust MN patches. This integrated system provides rapid, reactive oxygen species-responsive curcumin release along with sustained SDF-1α delivery, achieving spatially targeted penetration and localized drug deposition in the infarcted myocardium. In vitro studies demonstrated that curcumin-hydrogel effectively reprogrammed macrophage polarization from pro-inflammatory M1 to reparative M2 phenotype, downregulating pro-inflammatory cytokines while upregulating anti-inflammatory cytokine. Simultaneously, sustained SDF-1α release promoted endothelial cell proliferation, migration, and tube formation via VEGF pathway activation. In a rat MI model, the SDF-1α@Cur-MN patch significantly improved recovery of cardiac function, attenuated fibrosis, enhanced M2 macrophage infiltration, and promoted mature neovessel formation. This dual-target MN system provides a coordinated approach to regulating inflammation and angiogenesis, demonstrating therapeutic potential for myocardial repair.

Development of capsaicin loaded nanoparticles based microneedle patch for transdermal drug delivery

Background: Transdermal drug delivery by means of polymeric microneedles (PMNs) offers the advantage of overcoming some of the disadvantages of oral medication, such as first-pass metabolism, through painless, controlled drug release. Lawsone, isolated from Lawsonia inermis, exhibits reported antioxidant, anti-inflammatory, antimicrobial, and antitumor properties, suggesting its use as a promising candidate for topical application. Objectives: Fabrication and optimization of hyaluronic acid-carboxymethylcellulose (HA-CMC) PMNs loaded with lawsone with respect to enhancing transdermal delivery and understanding release and physicochemical characteristics. Methods: Hyaluronic acid-carboxymethylcellulose-lawsone patches were prepared by micromolding. The Box-Behnken design approach was then utilized to identify the appropriate concentrations of carboxymethylcellulose (CMC) (0.15% to 0.35% w/w), hyaluronic acid (HA) (0.01% to 0.09% w/w), and polyethylene glycol 400 (PEG 400) (0.5% to 1.5% w/w), all of which are dependent on drug release after 90 minutes. Morphological examination was conducted using light and scanning electron microscopy (SEM). The levels of transepidermal water loss (TEWL), drug content, insertion rate, mechanical properties, and release of the patches were assessed. Results: The optimized formulation showed a cumulative release of 59.63% in 90 min, following Higuchi release kinetics. Polymeric microneedles showed uniform morphology, a failure force of 0.48 N, full penetration of 375 μm, and reversible changes in TEWL. Conclusions: Hyaluronic acid-carboxymethylcellulose PMNs offer a promising formulation strategy for the transdermal delivery of lawsone. This preliminary study establishes a biocompatible platform with potential for future development towards anti-inflammatory and antitumor therapies, pending further in vivo validation.

PurposeNeurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease are debilitating conditions resulting from a progressive degeneration of nerve cells that is attributed to oxidative stress. Given the role of hydrogen sulphide (H2S), an endogenously produced signalling molecule involved in regulating of oxidative stress, exogenous administration of H2S has been proposed as a potential treatment strategy. This research study involved an investigation into the mechanical properties of microneedles loaded AP39 (a H2S donor), their ability to penetrate skin and effectiveness to deliver AP39 across murine skin. Additionally, the study explored the capability of permeated AP39 to release H2S and thus quench H2O2-induced oxidative stress in neuroblastoma cells, SHSY5Y cells.MethodsMicroneedles were prepared using 20% w/v polyvinyl alcohol (PVA) of either 27,000 or 67,000 molecular weights, with or without trehalose 15% w/v. Mechanical and insertion properties of microneedles were determined and optimised formulation applied to murine skin to observe AP39 flux through the skin. Collected media was applied to a microvasculature blood–brain-barrier model to evidence AP39 permeation, following which, permeated AP39 was applied to an oxidative stress scenario in SHSY5Y cells to assess AP39 potential in limiting oxidative stress.ResultsMicroneedle fracture testing observed the microneedles produced from polyvinyl alcohol 67,000 with trehalose were best able to withstand compression force applied. Microneedles formulated from PVA 67,000 were best able to penetrate the parafilm model. Further, the PVA 67,000 with trehalose microneedle formulation was observed to pierce murine skin and deliver 32.84 ± 2.11% of applied AP39 across the skin over 32 h. AP39 transport across the HUVEC microvasculature model gave an apparent membrane permeability of 18.6 ± 1.4. Finally, AP39 attenuated H2O2-induced oxidative stress as well as inflammation in SHSY5Y cells; resulting in reduced neurodegeneration burden.ConclusionThese findings demonstrate that microneedle patches for the transdermal delivery of AP39 may provide a promising clinical approach in the treatment of neurological disorder associated with oxidative stress.

The present study focused on the formulation and evaluation of Ketotifen Fumarate transdermal patches to overcome limitations of oral therapy, such as sedation and gastrointestinal side effects, and to enhance patient compliance through sustained drug delivery. Preformulation studies confirmed the drug’s characteristic organoleptic properties, including its white to off-white crystalline, odorless, and bitter-tasting nature. Eight transdermal patch formulations (KFT-P1 to KFT-P8) were prepared and assessed for critical parameters including pH (5.1–6.3), thickness (0.48–0.57 mm), weight variation (112.35–126.35 mg) and surface pH (5.4–5.8), all within skin-compatible ranges. Mechanical evaluations revealed strong folding endurance (77–98.24%), tensile strength (3.27–4.72 N/mm²), and moisture content (3.24–4.12%), indicating durability, flexibility, and adequate stability. Spreadability (4.45–6.95 g·cm/sec) ensured ease of application, while drug content was uniform (92.55–96.27%), confirming efficient drug loading. Physical appearance assessments highlighted smooth and flexible patches as most suitable for therapeutic use. Overall, the results demonstrate that Ketotifen Fumarate transdermal patches possess desirable physicochemical and mechanical attributes, making them promising candidates for sustained transdermal drug delivery.

Objective: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are essential part of the administration of Rheumatoid Arthritis (RA). Methotrexate (MTX) is effective for tumor necrosis factor alpha (TNF-a) biologic agents, indicated only in minority of patients suffering from severe RA. MTX remains the "anchor drug" in the treatment of RA. For delivery improvement, novel pharmaceutical drug delivery system i.e. MTX-Cubosomes were developed.
 Methods: Poloxamer 407 and Glycerol monooleate (Monoelin, MO) used and the formulation were characterized as a sustained release drug delivery system for Methotrexate. Different ratios of Monolein, Poloxamer 407 and water were used to develop the different cubosomes using homogenization and emulsification method. Characterization of formulations for morphology was performed and also particle size distribution by Transmission Electron Microscopy (TEM).
 Results: Formulation showed the internal cubic structures of the vesicles. The particle size of the formulations was found to be ranging from 53.21 to 185.32 nm, zeta potential of the formulations varied from-18.20-36.10 mV. The cubosomal formulation exhibited good entrapment efficiency along with high drug loading. Compatibility with the excipients was also established. An in vitro release study was done using Franz Diffusion cell indicated sustained release of the formulation at a rate of 1.25 %/h. Cubosomes proved to be reliable system for sustained transdermal drug delivery system.
 Conclusion: Methotrexate cubosomes is a novel medication delivery framework and in this examination it has been developed and characterized. The formulations were found to be promising in terms of its characterization parameters like particle size, zeta potential, entrapment efficiency, loading capacity, release kinetics, and stability, suitable for topical delivery.

Vesicular elastic liposomes for transdermal delivery of rifampicin: In-vitro, in-vivo and in silico GastroPlus™ prediction studies

Dissolving microneedles (DMNs) are emerging transdermal delivery platforms but rely on water-soluble polymers as carriers that inherently limit drug-loading capacity and slow release due to dissolution/diffusion barriers. Formulating drugs directly into robust DMNs is further challenged by crystallization tendencies. Here, a supramolecular engineering strategy enabling carrier-free antibiotic glass microneedles (GMNs) is presented, leveraging synergistic drug-sulfate-water interactions that suppress crystallization and form mechanically stable amorphous networks. Using tobramycin sulfate, monolithic GMNs are achieved with 100%-drug payload, exceptional strength (Young's modulus 5.1GPa), and instant transdermal delivery (threefold faster than polymer DMNs). Eliminating polymeric carriers accelerates drug diffusion by 2.6-fold, enabling deep tissue penetration for efficient biofilm eradication. In vivo evaluation demonstrates that the antibiotic GMNs effectively promote the healing of biofilm-infected skin wounds in mice and exhibit potent therapeutic efficacy against subcutaneous abscesses. This strategy extends broadly to aminoglycoside antibiotics. By replacing the polymer matrix with supramolecular-engineered amorphous networks, a next-generation DMN platform is pioneered that bridges critical gaps in drug-loading efficiency, dissolution kinetics, and clinical translation for urgent therapeutic applications.

This study investigates the usage of electrohydrodynamic (EHD)-3D printing for the fabrication of bacterial cellulose (BC)/polycaprolactone (PCL) patches loaded with different antibiotics (amoxicillin (AMX), ampicillin (AMP), and kanamycin (KAN)) for transdermal delivery. The composite patches demonstrated facilitated drug loading and encapsulation efficiency of drugs along with extended drug release profiles. Release curves were also subjected to model fitting, and it was found that drug release was optimally adapted to the Higuchi square root model for each drug. They performed a time-dependent and diffusion-controlled release from the patches and followed Fick’s diffusion law by the Korsmeyer–Peppas energy law equation. Moreover, produced patches demonstrated excellent antimicrobial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains, so they could be helpful in the treatment of chronic infectious lesions during wound closures. As different tests have confirmed, various types of antibiotics could be loaded and successfully released regardless of their types from produced BC/PCL patches. This study could breathe life into the production of antibiotic patches for local transdermal applications in wound dressing studies and improve the quality of life of patients.

Marine-derived polymers are increasingly recognized as versatile biomaterials for targeted drug delivery. This comprehensive review explores the sources, chemical structures, and pharmaceutical potential of key marine polymers, highlighting how their unique properties enable innovative drug delivery systems across multiple routes of administration. We classify major marine-derived polymers (e.g., alginate, chitosan, carrageenan, fucoidan, marine collagens) and explain their relevance based on biocompatibility, biodegradability, and functional diversity. We then examine their emerging applications in oral, buccal/sublingual, nasal, pulmonary, rectal, vaginal, ocular, and transdermal drug delivery, with two case studies per route illustrating recent preclinical or clinical advances. These case studies demonstrate how marine polymers enhance targeted delivery via mechanisms such as mucoadhesion, stimuli-responsive gelation, nanoparticle formation, and ligand-specific targeting. One illustrative graph and a summary table are included to visualize polymer classifications and key applications. The review also discusses recent innovations and patents, underscoring trends such as marine polymer-based nanocarriers for cancer therapy and microneedle patches for transdermal delivery. In conclusion, marine-derived polymers offer a rich platform for developing targeted, patient-friendly drug delivery systems. Their continued development, supported by growing clinical evidence and technological refinements, is poised to expand the pharmaceutical toolkit for precision medicine. Future prospects include scaled-up production, more in-depth safety profiling, and translational research to bring marine polymer-based delivery systems from bench to bedside. Keywords: Marine-derived polymers; Targeted drug delivery; Polysaccharides; Chitosan; Alginate; Carrageenan; Mucoadhesive delivery; Nanoparticles

Hyaluronic acid microneedle patch for transdermal delivery of naringin-loaded PEGylated terpesomes in a rat model of rheumatoid arthritis: Modulation TGF-β1, oxidative stress, and inflammation.