Search Results (897)

Dissolving microneedles (DMN) could be considered as a minimally invasive alternative for transdermal delivery of naltrexone hydrochloride (NTX). In the present study, DMN patches with smart design were developed via a two-step micromoulding technique. The systems were composed of drug-free polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) blend microneedle tips, combined with a drug-loaded backing layer based on PVP and Poloxamer 407. The influence of polymer concentration in DMN tips and backing-layer composition on morphology, mechanical properties, drug release and permeation was evaluated. Mechanical studies revealed that intermediate polymer concentration (formulation MN-20%/2:1) provided superior structural integrity (13.57 ± 1.43% height reduction after compression) and efficient penetration up to the fourth Parafilm^® layer. Incorporation of NTX into the backing layer allowed for high drug loading, while a 2:1 PVP:P407 ratio provided higher toughness (1806 g/mm) as well as thermoresponsive and controlled drug release. In vitro permeation studies demonstrated significantly enhanced NTX delivery from DMN systems compared to simple matrix patches—an almost 4-fold increase in flux with 56% permeation of NTX up to 8 h. These findings highlight the importance of polymer composition in DMN design and demonstrate the potential of the developed systems as an effective platform for transdermal delivery of NTX. Full article

Background: Oxidative stress contributes significantly to premature skin aging and inflammatory dermatological conditions. While plant-derived antioxidants have demonstrated considerable promise in topical applications, Bougainvillea glabra Choisy remains underexplored in standardized pharmaceutical dosage form development despite its documented phytochemical richness. Objective: This study aimed to develop, standardize, and characterize topical cold cream formulations incorporating B. glabra ethanolic leaf extract, with HPTLC-based quantification of marker compounds, validated antioxidant assessment, and preliminary dermal safety evaluation. Methods: The ethanolic leaf extract was prepared by maceration and characterized by preliminary phytochemical screening and HPTLC fingerprinting with quantitative densitometric analysis of quercetin and pinitol. Three cold cream formulations were developed at 10% (F1), 20% (F2), and 30% (w/w) (F3) extract loading. Formulations were evaluated for organoleptic properties, pH, homogeneity, spreadability, and viscosity. Antioxidant activity was assessed using a validated methanol extraction procedure followed by DPPH radical scavenging and potassium permanganate reduction assays. Ex vivo skin permeation was evaluated using Franz diffusion cells with freshly excised goat skin. Accelerated stability was conducted at 40 ± 2 °C/75 ± 5% RH for 90 days with HPTLC-based marker retention monitoring. Primary dermal safety was assessed in Wistar albino rats (n = 6) following OECD Test Guideline 404. Results: Quantitative HPTLC confirmed quercetin (4.82 ± 0.14 mg/g dry extract) and pinitol (2.31 ± 0.09 mg/g) as marker compounds, with linearly increasing content across F1–F3. All formulations demonstrated acceptable physicochemical properties (pH 5.7–5.9, viscosity 440,000–460,000 cP, spreadability 11.8 ± 0.3 cm·g/s). F3 exhibited the highest DPPH scavenging activity (56.68 ± 1.05%) with IC₅₀ of 1.3 ± 0.1% w/v, demonstrating a 3.2-fold improvement over F1. Extraction recovery from the cream matrix was 96.4–97.1%, validating the antioxidant data. Ex vivo quercetin permeation through goat skin reached 51.3 ± 2.8 μg/cm² at 24 h for F3, following Higuchi diffusion kinetics (R² > 0.99). No dermal irritation was observed (Primary Irritation Index = 0). Accelerated stability confirmed ≥98.3% retention of both marker compounds and antioxidant activity after 90 days. Conclusions: B. glabra leaf extract was successfully incorporated into a physicochemically stable, non-irritating cold cream with demonstrated dose-dependent antioxidant efficacy and cutaneous delivery capability. The study establishes preliminary dermal safety and in vitro antioxidant efficacy warranting further controlled clinical evaluation. Full article

Nanoplastics from plastic waste degradation pose a growing environmental health risk, yet size-dependent dermal effects remain poorly understood. This study investigated polystyrene nanoplastics of 50, 100, and 200 nm using ex vivo porcine skin and in vitro human keratinocyte models. Skin permeation, cellular uptake, viability, oxidative stress, inflammation, autophagy, and transcriptomic pathways were assessed. Enhanced nanoparticle penetration was observed in barrier-disrupted skin, primarily via hair follicles, with smaller particles showing greater intracellular accumulation. Transcriptomics revealed disruptions in oxidative stress, inflammation, endocytosis, and autophagy pathways. Specifically, 50 nm particles induced the strongest oxidative stress via Nrf2 activation and triggered sustained autophagy, leading to proliferation inhibition and time-dependent inflammation. In contrast, 100 nm particles caused moderate oxidative and inflammatory effects, whereas 200 nm particles provoked acute cytotoxicity, pronounced endocytosis, and an early inflammatory burst with subdued autophagy. These findings demonstrate that sub-100 nm PS NPs exhibit enhanced skin penetration in barrier-disrupted ex vivo models and induce pronounced oxidative stress, sustained autophagy, and proliferation inhibition in human keratinocytes. While these results suggest potential cellular mechanisms that may contribute to dermal toxicity, they do not directly demonstrate systemic absorption or long-term damage in vivo. Our observations provide a mechanistic basis for future in vivo investigations and highlight the need for caution when extrapolating in vitro findings to human health risks. Full article

Cosmetic preservatives should have reduced percutaneous absorption to lower the risk of systemic exposure and skin irritation. In this work, previously synthesized galactosylated derivatives of common cosmetic preservatives were comparatively evaluated for transdermal permeation and preliminary toxicity. Escherichia coli β-galactosidase was used to enzymatically modify several of the commonly used cosmetic preservatives to produce their corresponding galactosylated derivatives: benzyl alcohol β-d-galactopyranoside 7, 2-phenoxyethanol β-d-galactopyranoside 8, chlorphenesin β-d-galactopyranoside 9, 1,2-hexanediol β-d-galactopyranoside 10, 1,2-octanediol β-d-galactopyranoside 11, and 2-phenylethyl β-d-galactopyranoside 12. HPLC and NMR spectroscopy were used to analyze the previously synthesized derivatives. The Franz diffusion cell assay was used to evaluate skin penetration. 2-Phenoxyethanol (PE), chlorphenesin (CPN), and 2-phenylethanol (PhE), showed measurable skin penetration, with flux values ranging from 3.82 to 7.34 µg·h⁻¹·cm⁻² and permeability coefficients (Kp) between 1.38 and 3.00 × 10⁻³ cm·h⁻¹. In contrast, their galactosylated derivatives showed markedly reduced permeation under the same experimental conditions. Moreover, brine shrimp lethality assays indicated that galactosylated derivatives had significantly higher LD₅₀ values (1.6–2.1 mg/mL) than their parent compounds (0.1–0.79 mg/mL), suggesting lower cytotoxicity. These findings suggest that enzymatic galactosylation can significantly decrease skin permeability and the toxicity of cosmetic preservatives, highlighting its potential approach to improve the safety of cosmetic components. Full article

The skin serves as the first line of defense, being highly prone to external damage. Silibinin (SIL) exerts skin-protective properties, but its topical use requires a suitable delivery system. Despite the growing interest in proniosomal platforms loaded with natural products, their application for the cutaneous delivery of SIL remains scarcely explored. This study proposes the pharmaco-technical characterization and preclinical safety evaluation of a SIL-loaded proniosomal gel (SIL-PG) for skin application. SIL-PG was produced using the coacervation phase separation technique, analyzed in terms of physicochemical and technological properties, and evaluated in vitro and in ovo for potential cytotoxic and irritant effects. SIL-PG retained a yellowish, creamy aspect, proper rheological behavior and spreadability, gradual in vitro drug release, sustained permeation, and an adequate safety profile, evidenced by the lack of cytotoxicity in HaCaT keratinocytes and spheroids and the absence of irritant potential in 3D EpiDerm™ reconstructed human tissues and on the chorioallantoic membrane. Overall, these findings emphasize SIL-PG as a potential pharmaceutical formulation for dermal use, with favorable pharmaco-technical characteristics and in vitro–in ovo biocompatibility. Full article

Fucoidan (FPS), a sulfated polysaccharide isolated from brown algae with a molecular weight ranging approximately from 5 to 200 kDa, exhibits diverse bioactivities, yet its high molecular weight (HMW) restricts topical bioavailability. This study explored the molecular-weight-dependent transdermal behavior of FPS and its underlying interaction mechanisms with the skin barrier. To address this, FPS fractions (6 to 103 kDa) were prepared via controlled oxidative degradation. In vitro permeation studies combined with Confocal Laser Scanning Microscopy (CLSM) visualization revealed a critical molecular weight threshold of approximately 11 kDa. HMW-FPS were mainly retained on the skin surface, whereas low molecular weight FPS (LMW-FPS, ≤11 kDa) penetrated into the viable epidermis and dermis. ATR-FTIR spectroscopy was employed to elucidate the underlying mechanism, which revealed that LMW-FPS overcomes the skin barrier through synergistic structural modulations: (1) it enhances intercellular lipid fluidity, accompanied by a reduction in CH₂ stretching vibration intensity; (2) it induces conformational changes in keratin via direct electrostatic interactions, promoting the transition from α-helices to β-sheets. Furthermore, histological evaluation confirmed that FPS treatment caused no obvious skin irritation. These findings demonstrate that LMW-FPS acts as a safe, reversible modulator of the stratum corneum (SC) barrier, providing a promising strategy for the design of polysaccharide-based transdermal delivery systems. Full article

Pomegranate peel, an abundant agro-industrial by-product, represents a sustainable source of bioactive polyphenols, particularly punicalagin, which has been associated with antioxidant and photoprotective potential. This study aimed to develop microemulsions (MEs) containing pomegranate peel extract for dermal delivery of punicalagin using biocompatible surfactant systems. Three MEs differing in surfactant–cosurfactant composition (ME-A, ME-P, and ME-E) were prepared. Each formulation solubilized 1% (w/w) of pomegranate peel extract and was evaluated regarding in vitro release behavior, skin permeation/retention, antioxidant activity, and in vitro sun protection factor (SPF). All investigated MEs provided sustained release of punicalagin (≈10–17% of the applied dose in 8 h). ME-A, based on an alkyl polyglucoside surfactant, showed a significantly higher cumulative release of punicalagin (60.4 µg/cm²) compared with ME-E and ME-P. In skin penetration/permeation studies, ME-A also exhibited the highest numerical total delivery of punicalagin (≈48.2 µg/cm² after 24 h), although differences among formulations were not statistically significant. All formulations demonstrated high antioxidant activity in the DPPH assay and measurable in vitro photoprotective potential, with SPF values ranging from approximately 11 to 14. Overall, pomegranate peel extract-loaded MEs showed potential as dermal delivery systems capable of improving solubilization and modulating skin delivery of punicalagin. The combination of agro-waste-derived bioactives with biocompatible surfactants highlights the potential of these systems as sustainable approaches for skincare formulations. Full article

Background: Caffeine, although widely used in dermatological and cosmetic products, exhibits limited permeability through the stratum corneum, highlighting the need for strategies for optimizing delivery. The aim of this study was in vitro investigation of the effects of probiotic bacterial lysates and submicellar concentrations of bile acids on caffeine permeation, with a particular focus on permeation kinetics. Methods: Caffeine permeability was evaluated using the Skin Parallel Artificial Membrane Permeability Assay (Skin-PAMPA). Donor and acceptor concentrations were quantified by HPLC at predefined time points (1, 2, 4, 6, and 12 h), followed by calculation of apparent permeability coefficients, cumulative permeation profiles, and interval permeation rates in systems containing probiotic lysates and submicellar concentrations of cholic acid (CA) or deoxycholic acid (DCA). Results: Probiotic lysates significantly reduced caffeine permeability (0.98 ± 0.02 × 10⁻⁶ vs. 1.57 ± 0.14 × 10⁻⁶ cm/s in the control group) and modified transport kinetics resulting in lower early-phase interval permeation rates and reduced cumulative permeation. Conversely, bile acids increased the apparent permeability of caffeine, with the highest value observed in the DCA group (2.30 ± 0.08 × 10⁻⁶ cm/s). Conclusions: Overall, probiotic lysates and bile acids modulated caffeine permeation across the Skin-PAMPA membrane primarily by reshaping permeation kinetics rather than simply changing overall permeability. Their combined effects may provide a basis for designing topical formulations with tailored permeation profiles. Full article

Background/Objectives: Carprofen (CP) is a potent non-steroidal anti-inflammatory drug whose clinical use is limited by systemic adverse effects associated with oral administration. The aim of this study was to develop and evaluate a CP-loaded nanoemulsion (CP-NE) as a topical formulation for the management of post-surgical inflammation in veterinary applications. Methods: CP-NE was physicochemically characterized in terms of droplet size, polydispersity index, morphology, pH, rheological behavior, spreadability, and stability. Biopharmaceutical performance was assessed through in vitro drug release and ex vivo permeation studies using porcine ear skin. Safety was evaluated using in vitro cytotoxicity assays in HaCaT keratinocytes, histological analysis of ex vivo porcine skin, and assessment of biomechanical skin parameters in mice. Finally, anti-inflammatory efficacy was investigated in a murine model. Results: CP-NE showed a mean droplet size of approximately 140 nm, low polydispersity, spherical morphology, and Newtonian flow behavior with good spreadability. Stability studies confirmed the absence of significant physical destabilization and acceptable chemical stability under refrigerated and room temperature conditions. Release studies demonstrated sustained drug release, while permeation assays revealed low systemic exposure and high drug retention within the skin. Safety evaluations indicated good biocompatibility with no cytotoxicity, no histological alterations in skin tissue, and no alteration of the skin’s biomechanical properties in volunteers. In vivo efficacy studies showed that CP-NE significantly reduced post-surgical inflammation, promoting faster restoration of skin architecture and improved wound appearance. Conclusions: These findings suggest that CP-NE represents a promising topical delivery system for localized anti-inflammatory therapy following surgical procedures, offering significant potential for veterinary applications. Full article

Background/Objectives: Cannabis sativa is the source of cannabidiol (CBD), a non-intoxicating phytocannabinoid with analgesic and anti-inflammatory qualities that has demonstrated therapeutic potential in inflammatory skin conditions like dermatitis. However, low bioavailability and poor water solubility restrict its topical application. This study attempted to improve CBD solubility and transdermal delivery using an amorphous solid dispersion (ASD)-based hydrogel system. Methods: CBD was stabilized in its amorphous form using an ASD strategy and incorporated into a hydrogel matrix. The CBD-ASD hydrogel was characterized by particle size analysis, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), rheological assessment, swelling studies, and diffusion experiments using Franz cells. Biological evaluations included cytotoxicity testing in human dermal fibroblast (HDF) cells, wound-healing assays, RT-qPCR-based anti-inflammatory analysis, antioxidant activity (DPPH assay), and antibacterial testing against Staphylococcus aureus. Results: Physicochemical analyses confirmed successful amorphous dispersion of CBD within a stable hydrogel network. The formulation exhibited sustained drug release over 144 h, achieving 86.32% cumulative release with diffusion-controlled kinetics. Rheological and swelling properties demonstrated mechanical stability and hydration suitability for long-term topical application, while Franz diffusion studies confirmed effective transdermal permeation. The CBD-ASD hydrogel showed no cytotoxicity in HDF cells and significantly enhanced wound closure. It also downregulated pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Additionally, the formulation demonstrated 65.63 ± 10.00% DPPH radical scavenging activity and over 99% antibacterial inhibition. Conclusions: The CBD-ASD hydrogel represents a stable, multifunctional delivery platform that overcomes CBD solubility limitations and enhances therapeutic efficacy for inflammatory skin diseases. Full article

A hybrid method combining biomimetic liquid chromatography with immobilized artificial membrane (IAM) and quantitative structure–activity relationships (QSARs) was used to derive helpful models for predicting selected properties related to distribution (binding to human serum albumin (log P_w/HSA)) and absorption (skin permeation (log K_w/sp), plant cuticle permeation (log P_w/pc), and human intestinal permeability (Caco-2)), and therefore influencing the effectiveness or unwanted effects of 199 synthetic compounds that are regarded as potential drugs or plant protection products. The molecules under investigation—derivatives of 5H-6,7-dihydroimidazo [2,1-c][1,2,4]triazole, 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-one, 2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-dione, 1H-1,2,4-triazole, carbamic and phenoxyacetic acid—differ in their properties but all meet the requirements for xenobiotics to be considered as medicinal products. Reliable high-concept models were developed, indicating lipophilicity, molecular size, electronic properties, and the number of rotatable bonds as descriptors that determine the biological properties of these compounds. These models have been optimized and cross-validated, confirming their reliability and high predictivity. Full article

Background/Objective: The introduction of Ketoconazole (KZ, Nizoral^®) in 1977 by Janssen Pharmaceutica marked a significant milestone in medical mycology as the first broad-spectrum oral antifungal agent. However, KZ is a highly lipophilic compound, presenting significant challenges in the development of efficient topical formulations. Moreover, oral KZ has undergone labeling revisions and market withdrawal due to serious hepatic side effects. This study aimed to design, optimize, and evaluate KZ-loaded nanoemulsions (NEs; KZ-NEs) as a delivery platform that could improve skin bioavailability and antifungal activity. Methods: Optimized KZ-NEs were converted to a mucoadhesive formulation (KZ-NEC) by the addition of Carbopol^® 940 NF to enhance the adherence of the formulations to the skin surface. NEs were evaluated concerning physical appearance, globule size, polydispersity index, zeta potential, pH, viscosity, and drug content. Optimized KZ-NE and lead KZ-NEC formulations were further evaluated for in vitro release, ex vivo skin permeation and deposition, skin irritation, and in vivo studies. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KZ over 24 h. The ex vivo permeability coefficients of KZ from the optimized KZ-NE and lead KZ-NEC formulations were approximately four- and three-fold greater than that achieved with the marketed cream formulation, respectively. In addition, the C_max of the lead KZ-NEC formulation (14.4 ± 1.1 μg/mL) was significantly higher (p < 0.05) compared with the marketed cream formulation (10.5 ± 0.5 μg/mL). Moreover, in vitro antifungal susceptibility testing showed that KZ demonstrated improved antifungal efficacy when incorporated into the KZ-NE and KZ-NEC formulations. Neither of the NE-based formulations caused any alterations in skin color or morphology during the 24 h visual observation period. Both NE-based formulations were stable for 90 days (the last time-point tested) at three different storage conditions. Conclusions: NE-based formulation could serve as an effective topical delivery platform for KZ and could improve therapeutic outcomes for patients with topical fungal infections. Full article

This article represents the initial preformulation stage of a broader project aimed at evaluating polysiloxane films as carrier matrices for the TIODIN components thiamine bromide (ThBr) and sodium iodide (NaI). The specific gap addressed in this first part is the lack of information on how these two highly water-soluble crystalline salts are incorporated into hydrophobic crosslinked PDMS-based matrices, how they are distributed within such films, what solid-state forms and interactions may arise, and how these features relate to their release behaviour. Crosslinked films were prepared from α,ω-dihydroxypolydimethylsiloxane (PDMS–OH) of different viscosities, tetraethoxysilane (TEOS), and Sn(Oct)₂ as a catalyst. Raman spectroscopy, confocal Raman depth profiling, and X-ray diffraction showed that the films contain both individual ThBr and NaI crystallites and mixed crystalline domains consistent with partial ThBr/NaI association and/or iodide-exchanged phases. The fraction of such mixed domains was higher in films prepared from lower-viscosity PDMS–OH than in films based on higher-viscosity PDMS–OH, and depth profiling extended this trend into the accessible near-surface layers from both film sides. Release into physiological saline, used here as a simple comparative aqueous release medium, remained low, reaching approximately 9% for ThBr and 20% for NaI after 72 h, while film swelling was minimal, approximately 1–1.5%. These findings are consistent with restricted water penetration and diffusion-limited release from hydrophobic, weakly swelling matrices. Because this first part of the study is restricted to matrix characterisation, depth profiling, and release into saline, the present results should be regarded as preformulation data. They do not demonstrate skin permeation, therapeutic transdermal performance, or suitability as a complete patch dosage form but establish baseline structural and release characteristics for a planned Part 2 focused on more application-oriented film optimisation, including properties required for future transdermal patch development. Full article

Background: Apremilast (APM) is a selective phosphodiestrase-4 (PDE-4) inhibitor currently administered orally for the treatment of psoriasis. However, gastrointestinal irritation, frequent dosage regimens, and patient noncompliance limit its oral administration. Additionally, the poor permeability and solubility of APM make dermal administration challenging. Objective: The current study aims to formulate an optimized APM-loaded nanoemulsion formulation (APM-NE) to enhance drug delivery to deep psoriatic skin layers, thereby increasing dermal drug concentration for the effective treatment of psoriasis. Method: Using the phase titration method, the nanoemulsion (NE) was made with Capryol 90, Tween 20, and Labrasol as oil, surfactant, and co-surfactant, respectively. Results: The optimized formulation (F5) exhibited favorable physicochemical properties: mean droplet size of 147.4 ± 2.4 nm, and an entrapment efficiency (EE) reaching 86.30 ± 2.54%. TEM confirmed spherical, uniformly distributed droplets. In vitro release (86.1 ± 0.24%) followed zero-order kinetics. To enhance skin retention, F5 was incorporated into 2% Carbopol 980 gel, yielding F5G with pseudoplastic flow. Ex vivo permeation showed significantly higher drug delivery for F5 (1266.50 ± 5.6 µg/cm²) and F5G (1057.7 ± 6.76 µg/cm²) compared to crude APM gel (CR-APMG). In vivo, the inhibition of edema in rat paws was highest with F5G (66.83 ± 0.23%). RAW 264.7 cell studies showed 92.37% nitric oxide inhibition, and histopathology confirmed reduced inflammation. Conclusions: These results support APM-NE gel as a promising topical strategy for psoriasis therapy. Full article

In recent years, nanotechnology has made remarkable progress in the fight against infectious diseases. However, the development of safe and effective antiviral drugs remains a challenge, as viruses rely on host cells for replication. Plant-derived, environmentally friendly nanoparticles have gained significant attention due to their low toxicity, which enables them to target viruses without damaging host cells. In this study, we describe the synthesis of silver nanoparticles (AgNPs) using Arctostaphylos uva-ursi leaf extract and explore their potential antiviral activity. The uva-ursi AgNPs were initially characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). We then optimized two different gellan gum/alginate film formulations (1.6:0.4 and 1.2:0.8) as delivery matrices for the AgNPs and assessed Ag⁺ skin permeation using a Franz diffusion cell system. The antiviral potential of the uva-ursi AgNPs—both alone and incorporated into the films—was tested against herpes simplex virus type 1 (HSV-1). Our findings indicate that uva-ursi AgNPs may directly interact with the viral envelope, disrupting the lipid membrane and/or interfering with viral surface proteins. Overall, green-synthesized uva-ursi AgNPs may represent a natural, cost-effective, and safe alternative strategy for managing herpetic infections. Full article