Search Results (580)

Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic^® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm² of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC₅₀ for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article

Background/Objectives. Chronic inflammatory skin disorders, such as atopic dermatitis and psoriasis, require safe and effective topical treatments. This study aimed to develop and evaluate a novel anti-inflammatory emulsion enriched with menthol, capsaicin, amino acids (glycine, arginine, histidine), and boswellic acid. Methods. Three formulations were prepared: a control (E1), a partial (E2), and a comprehensive formulation (E3). Physicochemical analyses included texture profiling, rheological behavior, pH stability, moisture content, and particle size distribution. Results. E3 demonstrated superior colloidal stability, optimal pH (5.75–6.25), and homogenous droplet size (<1 µm), indicating favorable dermal delivery potential. Ex vivo permeation studies revealed effective skin penetration of menthol and amino acids, with boswellic acid remaining primarily in the epidermis, suggesting localized action. Under oxidative stress conditions, E3 significantly improved fibroblast viability, indicating synergistic cytoprotective effects of combined active ingredients. While individual compounds showed limited or dose-dependent efficacy, their combination restored cell viability to near-control levels. Conclusions. These findings support the potential of this multi-component emulsion as a promising candidate for the topical management of inflammatory skin conditions. Full article

Prunus leaf extracts are rich in phenolic and flavonoid compounds like rutin, and they are known for their antioxidant potential. This study compares the bioactivity and stability of leaf extracts from Prunus domestica L. (EL), Prunus salicina Lindl. (JL), and Prunus cerasifera Ehrh. (CL) and evaluates the dermal safety of a cream containing the extract with the most favorable in vitro properties for potential cosmetic use. Ethanolic extracts were assessed for total phenolic and condensed tannin contents, as well as antioxidants, using DPPH assay and lipid peroxidation inhibitory activities. The CL extract exhibited moderate total phenolic content, the highest condensed tannin content, and strong antioxidant (IC₅₀ = 22.1 ± 3.1 µg/mL) and anti-lipid peroxidation (62.3 ± 1.0%) activities. Based on these results, CL was incorporated into a cream formulation (CCL), which was then evaluated for physicochemical properties, antioxidant retention, and in vitro skin permeation using Franz diffusion cells. The formulation remained physically stable under ambient conditions and retained antioxidant activity above 74.5% under thermal cycling conditions. Rutin from the CCL formulation was retained within the Strat-M™ membrane (4.0 ± 1.1%), which was 5.7-fold higher than that of the control (0.7 ± 0.6%) over 8 h; however, it was not detected in the receptor chamber under these in vitro conditions. A semi-open patch test conducted on 26 healthy volunteers under double-blind conditions revealed no signs of irritation, confirming the formulation’s dermal safety. Overall, the findings support the feasibility of using P. cerasifera extract as a stable antioxidant component in topical skincare formulations. Full article

In this study, we designed an injectable skin-rejuvenating formulation based on polyethylene glycol–polycaprolactone–polyethylene glycol (PEG-PCL-PEG) copolymers to provide a synergistic combination of biocompatibility, antioxidative capacity, and regenerative potential. Through the systematic optimization of the precursor molar ratio and molecular weight, well-defined PEG-PCL-PEG copolymers were synthesized and structurally characterized using gel permeation chromatography (GPC), proton nuclear magnetic resonance (¹H-NMR), and Fourier transform infrared (FT-IR) spectroscopy. An optimized precipitation and drying protocol effectively reduced residual solvents, as confirmed by gas chromatography (GC). Idebenone was incorporated as an antioxidant to prevent skin aging, while hyaluronic acid (HA), L-arginine, and glycerin were included to promote collagen regeneration. In vitro assays demonstrated that idebenone-loaded samples exhibited prolonged intracellular antioxidant activity with low cytotoxicity. The collagen-promoting formulation, containing HA, glycerin, and L-arginine, enhanced the expression of transforming growth factor-β (TGF-β) and type III collagen (COL3) while suppressing inflammatory genes, suggesting a favorable environment for extracellular matrix remodeling. In vivo evaluation corroborated these outcomes, showing angiogenesis, collagen reorganization, and progressive dermal thickness. Histological analysis further confirmed sustained matrix regeneration and tissue integration. These results highlight the potential of PEG-PCL-PEG-based injectables as a multifunctional platform for collagen regeneration, offering a promising strategy for both cosmetic and clinical applications. Full article

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

The topical application of curcumin can act directly on the tissue, but there are problems related to solubility and permeation. Bigels combine hydrogels and organogels to enhance the release and transport of bioactives through the skin. The aim of this study was to develop bigels for the topical delivery of curcumin. Employing a rheology test, it was found that all bigels showed a solid-like behavior structure (G′ > G″) with stiffness increasing with higher organogel content. The principle of time–temperature superposition (TTS) was used to generate master curves. Microscopy revealed a morphological structure that depended on the organogel/hydrogel ratio. The bigels exhibited a pH compatible with that of human skin, and the curcumin content met the standards for uniform dosage. Thermal characterization showed the presence of three peaks in coconut oil bigels and two peaks in castor oil bigels. Bigels with a 45% castor oil organogel/55% hydrogel ratio exhibited a longer controlled release of curcumin, while bigels with coconut oil showed a faster release. The release data were fitted to mathematical models indicating non-Fickian release. The permeability of curcumin through Strat-M membranes was investigated, and greater permeation was observed with increasing organogel content. The developed bigels could be a promising option for the topical delivery of curcumin. Full article

The aim of this study was to develop double emulsions-filled chitosan hydrogel beads for topical application and to elucidate their skin penetration behavior. Double emulsions were prepared by a two-step emulsification method, and double emulsions-filled chitosan hydrogel beads were prepared by the extrusion method. The structure, stability, and skin penetration behavior were investigated. The results of yield efficiency (above 80%) and microstructure observation confirmed the feasibility of the preparation method. After loading the hydrophilic active ingredients (vitamin C) into this system, the retention ratio after storage for 6 weeks increased by 77.6%. Furthermore, hydrogel beads could promote the permeation of hydrophilic active ingredients loaded in double emulsions. When the concentration of chitosan was 3% (w/v), the permeation coefficient of vitamin C from hydrogel beads exhibited an increase (1.7-fold) compared with double emulsions. This system could affect the orderliness of lipid structures in the stratum corneum. In addition, the results indicated that this system could be used for the topical delivery of hydrophobic active ingredients (quercetin) as well. This is the first report of chitosan bead stabilization of W/O/W emulsions, yielding a 2.6-fold increase in skin uptake of hydrophilic actives. Full article

Background: Diclofenac is a phenylacetic acid derivative classified as a non-selective COX inhibitor. Similar to other NSAIDs, it is characterized by anti-inflammatory, antipyretic, and analgesic effects. Long-term therapy with diclofenac might also lead to severe gastrointestinal, renal, or cardiovascular systems disorders. Aim of the study was to compare own formulation prepared from pharmaceutical raw materials with ready-to-use diclofenac product. Methods: In the in vitro permeation experiments, human skin was excised from the abdomen of living patients as a result of plastic surgery. The transdermal semi-solid formulations were compounded using Pentravan^®, a ready-to-use transdermal base and hydrophilic gel base (Celugel). In vitro Penetration Studies, HPLC analysis, optical microscopy imaging, and a spreadability test were conducted. Rheological analysis provided insights into flow behavior, structure, and thixotropy. Results: Combination of Celugel with diclofenac sodium and the addition of substances acting as absorption enhancers, e.g., menthol, may provide an interesting alternative for enteral drugs, especially in patients with multimorbidity and polypharmacy. Conclusions: Topical diclofenac sodium with of addition of permeation enhancers like menthol might provide higher drug concentrations in the surrounding tissues and better analgesic and anti-inflammatory effects in compare to commercially available product and may provide optimum effectiveness with minimal risk of adverse effects, particularly in elderly and polymedicated patients. 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

Mild to moderate pain for a few hours to several days post-piercing is normal, and the pain is usually accompanied by swelling, redness, and warmth due to the inflammatory response. Cool compresses and over-the-counter analgesics (e.g., NSAIDs) can ease mild discomfort. However, oral NSAIDs may have systemic side effects; for this reason, we propose a topical anti-inflammatory approach. Four pranoprofen-loaded gels were created using different gelling agents: Sepigel^® 305 (PF-Gel-Sep), Carbopol^® 940 (PF-Gel-Car), Pluronic^® F-68 (PF-Gel-Plu), and Lutrol^® F-127 (PF-Gel-Lut). The gels were assessed for pH, morphology, FT-IR spectroscopy, rheological properties, spreadability, swelling and degradation, drug release kinetics, skin permeation (cow and human skin), irritation potential (HET-CAM assay), and impact on skin barrier function (TEWL and SCH). The gels exhibited varied rheological properties with PF-Gel-Car showing high viscosity and PF-Gel-Plu very low viscosity. All gels had similar spreadability with PF-Gel-Lut showing the highest. PF-Gel-Car showed the highest amounts of PF released, whereas PF-Gel-Plu led to the highest amount of pranoprofen retained in human and bovine skin. The HET-CAM assay indicated that none of the PF-Gels were irritating. Additionally, PF-Gel-Car and PF-Gel-Plu showed no cytotoxic effects on HaCaT cells. In vivo testing on mice showed that PF-Gel-Car prevented inflammation, while the rest of the gels were able to revert it in 25 min. Skin tolerance tests revealed the gels did not affect TEWL, and some gels improved SCH. The study successfully formulated and characterized four PF-loaded topical gels with potential to be used as an alternative for treating inflammation from piercings and ear tags. Full article

Onychomycosis, a fungal nail infection, affects about 4% of the global population. Current topical antifungals like ciclopirox and amorolfine have limited effectiveness, highlighting the need for better treatments. WSNS-PO is a novel water-soluble therapy designed to treat and prevent onychomycosis by enhancing nail health. This study evaluated WSNS-PO’s ability to penetrate the nail plate and to treat and prevent infection by Trichophyton rubrum using bovine hoof membranes and human nail clippings. The anti-fungal efficacy of WSNS-PO was additionally evaluated against other dermatophytes, non-dermatophyte fungi, and yeast. The results showed that WSNS-PO effectively permeated nails and reduced and prevented the colonization of human nail fragments by T. rubrum ex vivo, demonstrating an efficacy comparable to ciclopirox and amorolfine. WSNS-PO also prevented the transfer of T. rubrum infection between nails and inhibited the fungal colonization of human skin by dermatophyte and non-dermatophyte fungi and yeast. Together, these results indicate that WSNS-PO possesses fungistatic, barrier-forming, and anti-adhesive properties, suggesting that it holds promise as an onychomycosis treatment against dermatophytes, yeast, and molds. Full article

Caffeine is a well-known xanthine that possesses antioxidant effects that could contribute to its application in different skin disorders. In order to enhance its effects, approaches for improving its permeation and penetration through skin layers could be applied. This study emphasizes the preparation of caffeine–cyclodextrin complex and its formulation in carbopol hydrogel. The complex was developed at a 1:1 molar ratio between caffeine and hydroxypropyl-β-cyclodextrin. It was found that the complex enhanced the radical scavenging activity of caffeine against ABTS radical as well as the protective effects against H₂O₂-induced oxidative stress in L929 fibroblasts. Then, the complex was formulated in hydrogel by applying 1% carbopol. The spreadability and penetration of the loaded hydrogel were improved in comparison with the empty hydrogel. The results revealed that the system could be appropriate for therapies of skin disorders, and its wound healing abilities could be further investigated. Full article

Hydrogels (HDs) offer a promising platform for localized and sustained drug delivery. In this study, carboxymethyl chitosan (CMC)—based hydrogels were crosslinked with genipin and evaluated for the controlled release and tissue retention of suramin, a polyanionic drug with anti-inflammatory and antifibrotic properties. The influence of crosslinking density (1%, 3%, and 5%) on drug release, permeation kinetics, and retention was investigated using in vitro synthetic membranes and reconstructed human epithelial tissue models. The 1% genipin HD exhibited the highest cumulative release and drug retention (48.8 ± 6.8 μg/cm² in synthetic membranes; 24.06 ± 7.33 μg/cm² in epithelial models), along with a sustained release profile governed by first-order and Fickian diffusion kinetics. Notably, the 1% crosslinked formulation also demonstrated enhanced transmembrane flux (>140 μg/cm²/h after six hours), suggesting that lower crosslinking density favors both diffusional mobility and depot functionality. In contrast, free suramin solution displayed limited tissue interaction and minimal permeation, highlighting the role of the hydrogel matrix in regulating local bioavailability. These findings demonstrate that CMC–genipin HD can closely modulate drug delivery kinetics through crosslinking density, offering a biocompatible strategy for localized treatment of ulcerated epithelial conditions such as oral mucositis or chronic wounds. Diffusion models included a synthetic multilayer membrane (Strat-M^®) and a reconstructed human epidermis (EpiDerm™) to simulate skin-like barrier properties. 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/Objectives: Hormone Replacement Therapy (HRT) is commonly prescribed to women in need to restore the deficiency of hormones. Estrogens, in particular estradiol (E2) and estriol (E3), are associated with side effects when given orally. As such, estrogen is topically applied on the skin for the delivery of the hormone. The objective of this in vitro study is to evaluate the percutaneous absorption of compounded estradiol 0.06% and bi-est E3/E2 0.1%/0.06% in aqueous and anhydrous proprietary permeation-enhancing bases, in comparison with the commercially available estradiol transdermal gel (ESTROGel^®). Methods: The In Vitro Permeation Test (IVPT) was used and validated for the objectives of this study. The strength of estradiol/estriol in five test formulations was determined using Ultra Performance Liquid Chromatography (UPLC). Results: ESTROGel exhibited a rapid increase in the rate of skin absorption of estradiol within 0.5 h post-application. This peak was followed by a rapid decline in flux within 4 h, and then a slower decline by 16 h post-application. The initial rapid increase for ESTROGel was much faster than the rate of the four test compounded formulations, which each exhibited a slow and steady increase in the rate of skin absorption of estradiol with a peak flux within 6 h, and a steady absorption within 16 h of application. Conclusions: The compounded bases facilitated a steady percutaneous absorption of estradiol, without quick peaking or declining, which is one of the desired characteristics in HRT. Compounding pharmacists and practitioners may consider estradiol compounded formulations as a viable option for hormone delivery to patients. Full article