Search Results (814)

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

Transdermal drug delivery (TDD) is an increasingly important non-invasive method for administering active pharmaceutical ingredients (APIs) through the skin barrier, offering advantages such as improved therapeutic efficacy and reduced systemic side effects. As demand increases for patient-friendly and minimally invasive treatment options, TDD has attracted substantial attention in research and clinical practice. This review summarizes recent advances enhancing skin permeability through chemical enhancers (e.g., ethanol, fatty acids, terpenes), physical (e.g., iontophoresis, microneedles, sonophoresis), and nanotechnological methods (e.g., liposomes, ethosomes, solid lipid nanoparticles, and transferosomes). A comprehensive literature analysis, including scientific publications, regulatory guidelines, and patents, was conducted to identify innovative methods and materials used to overcome the barrier properties of the stratum corneum. Special emphasis was placed on in vitro, ex vivo, and in vivo evaluation techniques for such as Franz diffusion cells for assessing drug permeation and skin interactions. The findings highlight the importance of active physical methods, passive nanostructured systems, and chemical penetration enhancers. In conclusion, integrating multiple analytical techniques is essential for the rational design and optimization of effective transdermal drug delivery systems. 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

Background: Skin cancer has become a global health issue because of increasing exposure to environmental contaminants and UV radiation. Terbinafine hydrochloride (TRB), a broad-spectrum antifungal medication, has demonstrated notable anti-tumor properties in previous studies; however, its repurposing for skin cancer therapy remains underexplored. Objective: This study reports for the first time, the development of a new delivery system: a nanoemulsion (NE)–foam hybrid system, i.e., “nanoemulfoam” (NEF), designed to enhance the topical TRB delivery to the skin. The study applied this new hybrid system on TRB for managing skin cancer. Method: The TRB-loaded NEF was produced by loading TRB into a liquid NE. then this was incorporated into a liquid foam base and actuated into foam using a non-propellant mechanism. The NE was developed utilizing peppermint oil as the oil phase and Tween-20/ethanol as the surfactant/co-surfactant combination (Smix). The formulation underwent optimization using the D-optimal design that enabled the simultaneous evaluation of the impact of oil concentration and Tween 20 concentration in the Smix on the particle size (PS), zeta potential (ZP), and dissolution efficiency percent (DE%). Results: The optimal NE formula displayed a small PS of 186.60 ± 2.84 nm, ZP of −13.90 ± 0.99 mV, and DE% of 68.50 ± 1.78% (mean ± SD, n = 3). After incorporation into the foam system, the produced TRB-loaded NEF demonstrated a 7.43-fold increase in the drug transdermal flux in comparison with plain drug foam (p < 0.05). The TRB-loaded NEF showed no signs of inflammation or irritation when applied to abdominal rabbit skin, indicating its safety. The optimum formula exhibited a statistically significant 10-fold increase in cytotoxicity against A-431 skin cancer cells compared to TRB alone, along with a 1.54-fold increase in apoptosis (p < 0.05). Molecular docking studies targeting CDK2, a key regulator of cell proliferation and a known TRB target, revealed that TRB displayed highly favorable binding scores compared to the reference drug. Conclusions: The TRB-loaded NEF represents a promising nanotechnology-based approach for the topical treatment of skin cancer, supporting further investigation toward clinical translation. 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

Biomimetic peptides represent a growing class of active ingredients in modern cosmeceuticals, designed to mimic the function of the naturally occurring peptides involved in skin homeostasis, repair, and regeneration. Among them, acetyl hexapeptide-8 (AH-8), often referred to as a “botox-like” peptide, has received considerable attention for its potential to dynamically reduce wrinkles through the modulation of neuromuscular activity. AH-8 is widely used in topical formulations intended for anti-aging effects, scar treatment, and skin rejuvenation. This review provides a comprehensive overview of the structure and proposed mechanisms of action of AH-8, with particular focus on its efficacy and skin penetration properties. Due to its hydrophilic nature and relatively large molecular size, AH-8 faces limited permeability through the lipophilic stratum corneum, making effective dermal delivery challenging. Formulation strategies such as oil-in-water (O/W) and multiple water-in-oil-in-water (W/O/W) emulsions have been explored to enhance its delivery, but the ability of AH-8 to reach neuromuscular junctions remains uncertain. Preclinical and clinical studies indicate that AH-8 may reduce wrinkle depth, improve skin elasticity, and enhance hydration. However, the precise biological mechanisms underlying these effects—particularly the peptide’s ability to inhibit muscle contraction when applied topically—remain incompletely understood. In some studies, AH-8 has also shown beneficial effects in scar remodeling and sebum regulation. Despite promising cosmetic outcomes, AH-8’s low skin penetration limits its bioavailability and therapeutic potential. This review emphasizes the need for further research on formulation science and delivery systems, which are essential for optimizing the effectiveness of peptide-based cosmeceuticals and validating their use as non-invasive alternatives to injectable treatments. Full article

Human skin provides an effective route of delivery for selected drugs. Topical penetration of molecules is largely attributed to passive diffusion, and the degree of penetration can be represented by in silico, in vitro, and ex vivo models. Percutaneous absorption of pharmaceutical ingredients is a delicate balance between the molecular properties of the drug, the skin properties of the patients, and the formulation properties. Understanding this interplay can aid in the development of products applied to the skin. The kinetics of percutaneous absorption and an understanding of the rate-limiting steps involved can facilitate the optimization of these systems and enhance the degree to which skin drug delivery can be achieved. Solute–vehicle, vehicle–skin, and solute–skin interactions contribute notably to product release as well as the rate of absorption and diffusion across skin layers. These interactions alter the degree of permeation by interfering with the skin barrier or solubility and thermodynamic activity of the active pharmaceutical ingredient. This article aims to provide a concise understanding of some of the factors involved in the skin absorption of topical products, i.e., the pharmacokinetics of percutaneous absorption as well as the solute–vehicle–skin interactions that determine the rate of release of products and the degree of drug diffusion across the skin. Full article

Modern dermocosmetics combine the effectiveness of active substances with the benefits of percutaneous penetration enhancers to address skin issues such as hyperpigmentation. In this study, three bioactive tripeptides (with amino acid sequences CSF, CVL, and CSN) with previously confirmed tyrosinase inhibition activity were synthesized using the solid-phase synthesis method. The structures of the obtained peptides were determined. In addition, elastase in silico and in vitro inhibition assays were carried out. The tripeptides were subsequently encapsulated into liposomes, for which key physicochemical parameters were determined, including size, zeta potential, and encapsulation efficiency. The average diameter of the prepared liposomes was approximately 100 nm across all samples. The prepared carriers were found to be stable and exhibited no cytotoxicity toward reconstructed human epidermis cells. The peptides achieved an encapsulation efficiency of approximately 20–30%, with no significant differences observed between the cationic and anionic vesicles. Liposomes containing the CSF tripeptide, which showed the strongest tyrosinase-inhibiting effect, did not transport the peptide through the human skin in an ex vivo assay to permit quantification in the receptor solution, but facilitated penetration and retention of the tripeptide within the epidermis (4.65 ± 1.81 μg/cm²). These findings suggest that the prepared liposomes may serve as valuable carriers of bioactive tripeptides in anti-aging cosmetics. 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