Search Results (336)

Transdermal drug delivery offers a non-invasive route for the systemic and localized administration of therapeutics; however, the skin’s barrier function limits its efficiency. This study investigates the application of various electromagnetic field (EMF) configurations to enhance the transdermal delivery of salicylic acid, a model compound with moderate lipophilicity and ionizability. Samples were exposed to pulsed, oscillating, static, and rotating magnetic fields, and their effects on physicochemical properties, thermal stability, skin permeation, and accumulation were evaluated. Structural analyses (FTIR, XRD) and thermal assessments (TGA, DSC) confirmed that EMF exposure did not alter the chemical structure or stability of salicylic acid. In vitro transdermal studies using porcine skin and Franz diffusion cells revealed that pulsed magnetic fields—especially with a 5 s on/5 s off cycle—and rotating magnetic fields at 30–50 Hz significantly enhanced drug permeation compared to controls. In contrast, static fields of negative polarity increased skin retention, suggesting their potential for controlled, localized delivery. These findings demonstrate that EMFs can be used as tunable, non-destructive tools to modulate drug transport across the skin and support their integration into transdermal delivery systems aimed at optimizing therapeutic profiles. Full article

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. Full article

A transdermal drug delivery system based on hydrogel patches was explored, leveraging their sustained release properties and biocompatibility. Despite these advantages, conventional hydrogels often lack proper adhesion to the skin, limiting their practical application. To address this issue, we designed a skin-adhesive hydrogel using a polyacrylamide (PAM)/polydopamine (PDA) dual-network structure. The matrix combines the mechanical toughness of PAM with the strong adhesive properties of PDA, derived from mussel foot proteins, enabling firm tissue attachment and robust performance under physiological conditions. To demonstrate its applicability, the hydrogel was integrated with poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the hydrophobic antioxidant vitamin E as a model compound. The resulting PAM/PDA@VitE hydrogel system exhibited improved swelling behavior, high water retention, and prolonged release of α-tocopherol. These results suggest that the PAM/PDA hydrogel platform is a versatile vehicle not only for vitamin E, but also for the transdermal delivery of various cosmetic and therapeutic agents. Full article

Inflammatory skin diseases are highly prevalent conditions characterized by complex immune responses that result in skin tissue damage and pain, significantly impacting patients’ physical health. Traditional therapeutic approaches, including oral administration and injections, continue to exhibit inherent limitations. Consequently, there is growing interest in exploring alternative drug delivery systems that offer more effective, targeted, and patient-friendly therapeutic options. Transdermal administration emerges as a promising solution for managing inflammatory skin diseases, facilitating sustained drug release, and reducing the frequency of dosing. This review provides a comprehensive overview of the skin barrier and critically summarizes clinically adopted transdermal drug delivery systems (TDDSs), including sonophoresis, iontophoresis, chemical penetration enhancers, and electroporation. Particular emphasis is placed on emerging advances in microneedle- and nanocarrier-facilitated transdermal delivery strategies. Moreover, the article synthesizes recent fundamental evidence regarding the application of TDDSs in the treatment of atopic dermatitis, psoriasis, and acne. This review examines fundamental research evaluating various transdermal drug delivery systems for the treatment of major inflammatory skin diseases, with an emphasis on their mechanisms of action, advantages, challenges, and future directions. Transdermal drug delivery systems hold the potential to deliver more efficient and safer treatment and management strategies for patients afflicted with inflammatory skin diseases. Full article

Tannic acid (TA) possesses antioxidant, anticancer, and antibacterial properties. However, its pH sensitivity, protein cross-linking properties, and susceptibility to oxidation restrict its application. To address these challenges, W/O/W multiple emulsified TA microcapsules were developed using soybean protein isolate (SPI) as the natural wall material emulsifier through a two-step emulsification and spray drying process. The encapsulation efficiency of the obtained TA microcapsules was 87.6%, and TA’s thermal stability was significantly improved. TA microcapsules effectively reduced the acidity and irritability of TA, eliminated protein flocculation, and enhanced biocompatibility. Notably, the cell viability of the TA microcapsule (>94%) was significantly higher than free TA (65.6%). The storage stability test revealed that the microcapsules maintained structural integrity, with a retention rate of 96% after 10 days of storage. In vitro release studies of TA microcapsules demonstrated a sustained-release effect within 24 h. Simulated digestion studies further elucidated the protective effect of microcapsules on TA during gastric digestion. These multi-structured microcapsules based on SPI effectively address the limitations associated with TA utilization and enhance its potential for dual oral/transdermal administration in biomedical and cosmetic applications. Full article

This study investigates the Quality by Design (QbD)-driven development and optimization of a nanoemulgel incorporating Kunzea ericoides oil for transdermal therapy. Nanoemulgels enhance percutaneous drug delivery, sustain release profiles, and improve bioavailability. A central composite design was employed to optimize critical formulation parameters, with ANOVA confirming a statistically significant impact on particle size and drug release kinetics (p < 0.05). The optimized formulation exhibited a particle size of 112.38 nm, a polydispersity index of 0.203, and a zeta potential of −29.0 mV, ensuring colloidal stability. In vitro drug release followed the Higuchi model (R² = 0.989, kH = 4.776), indicating diffusion-controlled kinetics, while the Korsmeyer–Peppas model (n = 0.88) suggested an anomalous transport mechanism. Antibacterial studies determined minimum inhibitory concentrations of 250 µg/mL for Staphylococcus aureus and 500 µg/mL for Escherichia coli, indicating greater susceptibility in S. aureus. In vivo anti-inflammatory evaluation using a carrageenan-induced paw edema model demonstrated a statistically significant reduction in inflammation (p = 0.005 at 60 min), with a near-complete resolution by 240 min. These findings underscore the potential of Kunzea ericoides nanoemulgel as a promising transdermal therapeutic, integrating controlled drug release with potent anti-inflammatory and antibacterial properties for dermatological and inflammatory conditions. Full article

Microcirculation damage, dermal thickening, and difficulty in the spatiotemporal coordination of key platelet factor 4 (CXCL4) and transforming growth factor-β (TGF-β) contribute to the lack of effective treatments for systemic sclerosis (scleroderma, SSc). To address these challenges, we proposed a novel synergistic drug combination of ginsenoside Rk3 (CXCL4 regulator) and metformin (Met, TGF-β regulator) based on molecular docking and developed an ultra-long release, dual-target regulation hydrogel microneedle system (Rk3/Met URS MN). The rapidly dissolving tips of this hydrogel microneedle consisted of polyvinyl alcohol and polyvinylpyrrolidone, and were loaded with polydopamine-coated, coordination-induced self-assembled Rk3/Met nanomedicines. These micro-tips could spatiotemporally synchronize transdermal delivery of the hydrophobic Rk3 and hydrophilic Met, providing ultra-long release for up to 10 days with a single administration. The recombinant collagen CF-1552/oxidized pullulan-based (CAOP) hydrogel backing exhibited skin self-adhesiveness and excellent mechanical properties and could perform localized moisture retention and free radical scavenging at the lesion site. In vitro and in vivo efficacy studies, along with bioinformatics analysis of RNA sequencing, demonstrated that the Rk3/Met URS MN achieved immune modulation, anti-inflammatory effects, angiogenesis promotion, and antifibrosis in SSc through synergistic CXCL4/TGF-β dual-target regulation. Notably, on the 10th day, the dermal thickness decreased from 248.97 ± 21.3 μm to 152.7 ± 18.1 μm, with no significant difference from the normal group, indicating its significant potential in clinical applications in SSc. Full article

Gum rosin and its derivatives have been used traditionally in coatings and adhesives and are now increasingly applied in diverse medical and pharmaceutical fields. Owing to its film-forming ability, hydrophobic nature, biocompatibility, and ease of chemical modification, gum rosin has emerged as a promising excipient for controlled drug release, targeted drug delivery, and other biomedical applications. This review summarizes the evolution of gum rosin applications, from its conventional roles to its modern utilization in nanocarriers, transdermal systems, and other advanced drug delivery platforms. In addition, we discuss the challenges related to allergenicity, brittleness, and excessive hydrophobicity and propose strategies (such as chemical modification and polymer blending) to overcome these issues. This review provides a reference framework for researchers developing new rosin-based materials in pharmaceutical sciences. Full article

Background/Objectives: Raynaud’s phenomenon (RP) is characterized by an exaggerated vasoconstrictive response of small blood vessels in the fingers and toes to cold or stress. Oral therapy with tadalafil (TDL), a phosphodiesterase-5 inhibitor, is limited by systemic side effects and reduced patient compliance. This study aimed to develop and evaluate a TDL-loaded nanoemulgel for transdermal delivery as a non-invasive treatment alternative for cold-induced vasoconstriction. Methods: TDL-loaded nanoemulsions were prepared using the aqueous titration method with cinnamon oil as the oil phase and Cremophor RH40 and Transcutol as the surfactant–cosurfactant system. The optimized nanoemulsion was incorporated into a carbopol-based gel to form a nanoemulgel. The formulation was characterized for droplet size, morphology, thermodynamic stability, rheological properties, in vitro drug release, skin permeation, and pharmacokinetic behavior. Infrared thermography was employed to assess in vivo efficacy in cold-induced vasoconstriction models. Results: The optimized TDL nanoemulsion exhibited a spherical morphology, a nanoscale droplet size, and an enhanced transdermal flux. The resulting nanoemulgel displayed suitable physicochemical and rheological properties for topical application, a short lag time (0.7 h), and a high permeability coefficient (Kp = 3.59 × 10⁻² cm/h). Thermal imaging showed significant vasodilation comparable to standard 0.2% nitroglycerin ointment. Pharmacokinetic studies indicated improved transdermal absorption with a higher C_max (2.13 µg/mL), a prolonged half-life (t_1/2 = 16.12 h), and an increased AUC_0–24 compared to an oral nanosuspension (p < 0.001). Conclusions: The developed TDL nanoemulgel demonstrated effective transdermal delivery and significant potential as a patient-friendly therapeutic approach for Raynaud’s phenomenon, offering an alternative to conventional oral therapy. Full article

Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely constrained by non-targeted biodistribution. Pharmacokinetic analyses reveal prolonged dermal retention and suboptimal lesion accumulation, predisposing 42% of patients to phototoxic reactions. To address these limitations, this work creatively suggested a local targeted drug delivery method based on soluble microneedles in response to the difficulties mentioned above. The rational design of a molecular weight (MW) HA gradient system enabled the engineering of ternary nanocomposite microneedles with enhanced biomechanical integrity (0.49 N/needle) and superior HP loading capacity, which collectively facilitated spatiotemporally controlled transdermal delivery of hematoporphyrin with complete dissolution within 30 min. The release performance, skin permeability, and storage stability of hematoporphyrin dissolving microneedles (HP-DMNs) have all been demonstrated in vitro. This study applies soluble microneedle technology to the delivery of HP in PWS for the first time. It avoids the risk of systemic exposure through precise local administration. It uses the rapid dissolution properties of microneedles to achieve high concentration and rapid release of drugs in skin lesions. This study provides a new strategy for sustained intralesional release and rapid drug delivery treatment of PWS and provides novel ideas for the development of new formulations of HP and related photosensitizers. Full article

Background/Objectives: Polymeric nanofibers are promising platforms for skin treatment applications due to their large surface area and high porosity, which promote enhanced drug delivery. This study aimed to develop and compare poly(lactic acid)-based (PLA) nanofibrous mats, using linear PLA and a star-like PLA-pentaerythritol (PLA-PE) copolymer, as carriers for transdermal delivery of the antibacterial agent levofloxacin (LEV). Methods: Electrospinning was employed to fabricate nanofibers from PLA and PLA-PE solutions. Spinning parameters and polymer concentrations (10% w/v PLA and 20% w/v PLA-PE) were optimized to produce uniform fibers. LEV was loaded at 10% and 20% w/w. A sum of complementary characterization techniques, including scanning electron microscopy (SEM), infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC), were applied to comparatively investigate the fibers’ morphology, structural properties, and crystallinity. Drug loading, porosity, degradation, and in vitro release profiles were evaluated. Results: PLA-PE nanofibers demonstrated smaller diameters and higher porosity (up to 90.1%) compared to PLA (82.4%), leading to enhanced drug loading (up to 34.78%) and faster degradation (55% vs. 43% mass loss over 60 days). Drug release exhibited a biphasic profile with an initial burst followed by sustained release. PLA-PE formulations released up to 60.2% LEV, compared to 38.1% for PLA counterparts. Conclusions: The star-like PLA-PE copolymer enhances nanofiber properties relevant to the desired application, including porosity, degradation rate, and drug release. These findings suggest that PLA-PE is a promising material for developing advanced transdermal antibiotic delivery systems. Full article

External environmental stressors and internal physiological changes frequently compromise the skin barrier, resulting in conditions such as dermatitis and dehydration. A key underlying factor is the depletion of ceramides, essential lipids in the stratum corneum that maintain skin integrity. Although topical ceramide supplementation is effective for barrier repair, its clinical application is limited by poor solubility and low skin permeability. To overcome these challenges, this study developed an oil-in-water nanoemulsion (O/W-NE) using ultrasonic emulsification for the efficient transdermal delivery of ceramide C2. Octyldodecanol was selected as the oil phase to enhance ceramide solubility, while glycerin was incorporated to increase aqueous phase viscosity, reduce particle size, and function as a biocompatible penetration enhancer. The optimized nanoemulsion achieved a particle size of 112.5 nm and an encapsulation efficiency of 85%. Its performance was evaluated via in vitro release, ex vivo skin permeation, and in vivo biocompatibility studies. Mechanistic investigations revealed that both particle size and glycerin concentration significantly influenced ceramide penetration into the epidermis and dermis. Additionally, the nanoemulsion exhibited moisturizing and barrier-repair effects in a damaged skin model. Overall, this O/W-NE offers a stable, non-invasive strategy for enhancing ceramide delivery and restoring skin barrier function. Full article

Background: Hypertension (HTN) is recognized as a major risk factor for cardiovascular disease, chronic kidney disease, and peripheral artery disease. Valsartan (VAL), an angiotensin receptor blocker drug for hypertension, has been limited due to its poor solubility and poor absorption from the GIT, which leads to low oral bioavailability. Objectives/Method: In the present research, firstly, VAL-loaded nanoliposomes were formulated and optimized using the Box–Behnken design (BBD). Optimized VAL-nanoliposomes were physically characterized and their fate was examined by scanning and transmission microscopy, DSC, FTIR, XRD, and ex vivo studies using rat skin. In vitro studies using human keratinocyte (HaCaT) cells showed a decrease in cell viability as the liposome concentration increased. Secondly, the formulation of VAL-loaded nanoliposomes was integrated into dissolvable microneedles (DMNs) to deliver the VAL transdermally, crossing the skin barrier for better systemic delivery. Results: The optimized nanoliposomes showed a vesicle size of 150.23 (0.47) nm, a ZP of −23.37 (0.50) mV, and an EE% of 94.72 (0.44)%. The DMNs were fabricated using a ratio of biodegradable polymers, sodium alginate (SA), and hydroxypropyl methylcellulose (HPMC). The resulting VAL-LP-DMNs exhibited sharp pyramidal microneedles, adequate mechanical properties, effective skin insertion capability, and rapid dissolution of the microneedles in rat skin. In the ex vivo analysis, the transdermal flux of VAL was significantly (5.36 (0.39) μg/cm²/h) improved by VAL-LP-DMNs. The enhancement ratio of the VAL-LP-DMNs was 1.85. In conclusion, liposomes combined with DMNs have shown high potential and bright prospects as carriers for the transdermal delivery of VAL. Conclusions: These DMNs can be explored in studies focused on in vivo evaluations to confirm their safety, pharmacokinetics profile, and pharmacodynamic efficacy. Full article

Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. This study developed a sustained-release hydrogel microneedle patch encapsulating GeXIVA[1,2] to address these challenges. Optimized 4:3 (w/w) polyvinyl alcohol (PVA)–sucrose hydrogel formulation achieved 98.6% structural integrity and controlled swelling (ratio = 1.9 at 48 h). The microneedles demonstrated uniform conical morphology (height: 889 ± 49 µm, base: 381 ± 26 µm) enabling epidermal penetration. In spared nerve injury (SNI) models, a single microneedle patch application increased mechanical paw withdrawal thresholds from 0.056 g to 0.7269 g, maintaining efficacy for 3 days. Chronic constriction injury (CCI) models showed comparable pain relief. Notably, microneedle patch treatment improved locomotor function in SNI mice (total movement: 1518 cm vs. 1126 cm untreated). This hydrogel microneedle patch platform extends GeXIVA[1,2]’s analgesic duration from hours to days through sustained release, while resolving administration challenges through transdermal delivery, expanding the potential applications of GeXIVA[1,2], and demonstrating a promising strategy for the chronic neuropathic pain management. Full article

A polyvinyl alcohol (PVA) matrix hydrogel loaded with Centaurea cyanus extract was created for transdermal wound healing. Secondary metabolites, antibacterial properties, and the cytotoxicity of C. cyanus extract were investigated. The secondary metabolite profiles of the extract were determined by liquid chromatography–mass spectrometry (LC-MS) technique. It was determined that the extract has metabolites such as quinic acid, caffeoylquinic acid, kaempferol, etc., which contribute to the steps of wound healing. The extract had significant activity against Staphylococcus aureus when compared with ampicillin antibiotic and showed an inhibition zone of 16.9 mm ± 0.8, whereas ampicillin’s inhibition zone was 15.8 mm ± 0.8. The extract did not exhibit cytotoxic effects on 3T3-L1 (CL173) healthy skin fibroblasts, maintained cell viability for 72 h, and exhibited a 19% proliferative effect. Fourier-transform infrared spectroscopy, scanning electron microscopy, ultraviolet visible spectrophotometer, tensile strength analyses, in vitro release, and physicochemical tests were conducted. It was seen that the surfaces of the samples are smooth and homogeneous, patches had a significant amount of water absorption capacity, and 79% of the extract was released within the first 24 h of application; consequently, these results indicate that C. cyanus might be used in wound healing with its antibacterial, growth-promoting properties. Full article