Search Results (344)

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: The work presented herein focused on the development and characterization of a transdermal caffeine platform fabricated from ultrathin micro- and submicron fibers produced via electrospinning. Methods: The formulations incorporated caffeine encapsulated in a polyethylene oxide (PEO) matrix, combined with various permeation enhancers. A backing layer made of annealed electrospun polycaprolactone (PCL) facilitated the lamination of the two layers to form the final multilayer patch. Comprehensive characterization was conducted, utilizing scanning electron microscopy (SEM) to assess the fiber morphology, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) for chemical detection and to assess the stability of the caffeine, and differential scanning calorimetry (DSC) along with wide-angle X-ray scattering (WAXS) to analyze the physical state of the caffeine within the fibers of the active layer. Additionally, Franz cell permeation studies were performed using both synthetic membranes (Strat-M) and ex vivo human stratum corneum (SC) to evaluate and model the permeation kinetics. Results: These experiments demonstrated the significant role of enhancers in modulating the caffeine permeation rates provided by the patch, achieving permeation rates of up to 0.73 mg/cm² within 24 h. Conclusions: This work highlights the potential of using electro-hydrodynamic processing technology to develop innovative transdermal delivery systems for drugs, offering a promising strategy for enhancing efficacy and innovative therapeutic direct plasma administration. 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

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

Quercetin (Que) is widely recognized for its antioxidant and neuroprotective properties; however, its clinical potential remains limited due to poor solubility and low oral bioavailability. Nasal powders have emerged as a promising strategy to overcome these limitations, taking advantage of nose-to-brain delivery, offering a direct, non-invasive route to the central nervous system while bypassing first-pass metabolism. This study aims to extend previous work by systematically investigating the impact of different preparation methods (spray drying vs. lyophilization) and the incorporation of hydroxypropyl methylcellulose (HPMC) and mannitol/lecithin microparticles (MLMPs) on the physicochemical characteristics, structural properties, and in vitro diffusion behavior of HPβCD-based nasal powder formulations of Que. Thermal behavior and stability were analyzed using TGA, while morphology and particle distribution were assessed via Scanning Electron Microscopy. In vitro diffusion studies using Franz cells and regenerated cellulose membranes were conducted under simulated nasal conditions. Among all tested formulations, the spray-dried HPβCD/Que powder (F4) showed the highest permeation (0.11 ± 0.01 mg/cm² at 120 min). The inclusion of HPMC improved thermal stability but reduced Que diffusion, likely due to increased viscosity and matrix formation. Blending with MLMPs enhanced powder flow and dose placement, although it modestly reduced diffusion efficiency. Overall, this study highlights the potential of HPβCD-based spray-dried powders for nasal Que delivery and demonstrates how HPMC and MLMPs can be strategically employed to tailor performance characteristics. Full article

Background/Objectives: The treatment of atopic dermatitis frequently involves using a topical corticosteroid and a moisturizer. While the sequential application of these products is a common dermatological practice, their influence on drug penetration remains poorly understood. There is no clear evidence on how hydration, application sequence, and massage affect cutaneous drug delivery. Hence, this study aimed to evaluate the effects of formulation type, moisturizer composition, application sequence, and mechanical stimulation on betamethasone dipropionate (BET) cutaneous penetration. Methods: Two commercial formulations (cream and ointment) of BET were evaluated in different experimental conditions, including drug application combined with moisturizers (Cetaphil^®, as an emollient; Nivea^®, as an occlusive) pre- or post-application, with or without a 30 s massage. In vitro skin penetration assays were conducted for 12 h using porcine skin mounted in modified Franz diffusion cells. BET levels were extracted from the skin layers and quantified by HPLC. Results: The cutaneous BET penetration was strongly influenced by the application sequence, type of moisturizer, and mechanical stimuli. Pre-application of an occlusive or emollient moisturizer, followed by 30 s physical stimuli, significantly enhanced drug retention in the stratum corneum. For the cream, pre-application of moisturizers followed by massage notably increased BET levels in both the stratum corneum and viable skin. Conversely, post-application of moisturizers hindered BET absorption. The ointment showed limited penetration across all conditions, with no drug detected in the viable skin. Conclusions: The results showed pre-hydrating the skin, combined with a 30 s massage, was the best strategy for BET diffusion into the skin following cream administration. The formulation type and the order of application directly influence the effectiveness of drug therapy and the topical absorption of BET. Full article

Background/Objectives: This study investigates the physical, rheological, and antioxidant properties of nano-liposomal formulations encapsulating Fumaria officinalis L. (fumitory) extract, focusing on their stability and performance under ultraviolet (UV) exposure, as well as polyphenol release within simulated skin conditions in a Franz diffusion cell. Methods: Liposomal formulations, composed of phospholipids with or without β-sitosterol or ergosterol, were evaluated for their encapsulation efficiency, liposome size, size distribution, zeta potential, viscosity, surface tension, density, oxidative stability, antioxidant capacity, and polyphenol recovery. Results: Encapsulation efficiency was the highest in phospholipid liposomes (72.2%) and decreased with the incorporation of sterols: 66.7% for β-sitosterol and 62.9% for ergosterol liposomes. Encapsulation significantly increased viscosity and reduced surface tension compared to the plain liposomes, suggesting modified interfacial behavior. The inclusion of fumitory extract significantly increased the viscosity of liposomes (from ~2.5 to 6.09–6.78 mPa × s), consistent with the observed reduction in particle size and zeta potential. Antioxidant assays (thiobarbituric acid reactive substances—TBARS, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid—ABTS, and 2,2-diphenyl-1-picrylhydrazyl—DPPH) confirmed enhanced lipid peroxidation inhibition and radical scavenging upon encapsulation, with ABTS activity reaching up to 95.05% in sterol-containing liposomes. Release studies showed that the free extract exhibited the fastest polyphenol diffusion (5.09 × 10⁻⁹ m²/s), while liposomes demonstrated slower/controlled release due to bilayer barriers. UV-irradiated liposomes released more polyphenols than untreated ones, particularly in the sterol-containing formulations, due to oxidative destabilization and pore formation. Conclusions: These findings highlight the potential of fumitory extract-loaded liposomes as stable, bioactive carriers with tunable polyphenol antioxidant release properties for dermal applications. Overall, liposomal formulations of fumitory extract exhibit significant potential for further development as a pharmaceutical, cosmetic, or dermo-cosmetic ingredient for use in the prevention and treatment of various skin disorders. Full article

Objectives: Ex vivo nasal mucosa models provide physiologically relevant platforms for evaluating nasal drug permeability; however, their application is often limited by high experimental variability and the absence of standardized methodologies. This study aimed to improve experimental design by addressing two major limitations: the confounding effects of mucosal thickness and the questionable reliability of fluorescein sodium (Flu-Na) as an integrity marker for chemically induced mucosal injury. Methods: Permeability experiments were conducted using porcine nasal tissues mounted in Franz diffusion cells, with melatonin and Flu-Na as model compounds. Tissues of varying thickness were collected from both intra- and inter-individual sources, and a numerical simulation-based method was employed to normalize apparent permeability coefficients (Papp) to a standardized mucosal thickness of 0.80 mm. The effects of thickness normalization and chemically induced damage were systematically evaluated. Results: Thickness normalization substantially reduced variability in melatonin Papp, particularly within same-animal comparisons, thereby improving statistical power and data reliability. In contrast, Flu-Na exhibited inconsistent correlations across different pigs and failed to reflect the expected increase in permeability following isopropyl alcohol (IPA)-induced epithelial damage. These results suggest that the relationship between epithelial injury and paracellular transport may be non-linear and not universally applicable under ex vivo conditions, limiting the suitability of Flu-Na as a standalone marker of mucosal integrity. Conclusions: The findings highlight the importance of integrating mucosal thickness correction into standardized experimental protocols and call for a critical reassessment of Flu-Na in nasal drug delivery research. Full article

Oral administration of dipyridamole (DIP) with acetylsalicylic acid (ACA) is recommended in thromboembolic conditions or for the treatment of myocardial infarction and stroke. The present study presents an alternative dosage form of these two active ingredients, consisting of a honey core and a dark chocolate coating. The composition masks the bitter taste, is palatable and ensures compliance of a wide range of patients, mainly pediatric. For the simultaneous quantitative determination of the analytes, a Diode Array Detector/Fluorescence Detector (HPLC-DAD/FLD) method was used with a C18 column (250 mm × 4.6 mm, 5 μm) and an isocratic two-phase system (A: H₂O 0.2% formic acid—B: Acetonitrile-H₂O 90:10 v/v) 65:35 v/v. The method was validated according to ICH guidelines (r² > 0.999, RSD < 2.3%, % Recovery > 95.4%), and a stability study of the two active ingredients as well as salicylic acid (SAL), which is a hydrolysis product of ACA, was followed. Finally, a digestion protocol (oral cavity–stomach–intestine) for edible materials was applied to determine the release rate of ACA, DIP and SAL in the gastrointestinal tract, while an in vitro permeability study (P_app) was subsequently performed in Franz cells. The results show satisfactory behavior of ACA and DIP and provide a trigger for further studies of the formulation. Full article

Background/Objectives: Reverse iontophoresis (R-IP) is a technology that transdermally delivers components from inside the body to outside the body using electroosmotic flow (EOF) generated by applying a low electric current through the skin. It has attracted attention as a non-invasive sampling method for therapeutic drug monitoring (TDM). The purpose of this study was to determine whether urea and Tween 80 effectively enhance drug extraction from beneath the skin using R-IP. Methods: An in vitro drug extraction test using hairless mouse skin and R-IP was performed with a 3-chamber Franz cell and Ag|AgCl electrodes by applying a constant current (0.25 mA/cm²) for 6 h. Acetaminophen was chosen as the model drug, and its solution (30, 100, or 300 μg/mL) was placed in the subdermal compartment. The pH of both the electrode and subdermal compartment solutions was maintained at 7.4. Results: Acetaminophen was gradually extracted into the electrode compartment in a concentration-dependent manner and was more abundant in the cathode compartment than in the anode compartment. In addition, urea significantly promoted drug extraction, particularly on the cathode side, and a linear relationship was observed between the subdermal concentration and extracted amount. This effect is likely due to skin hydration caused by urea, which enhances EOF generation in the skin. Conversely, Tween 80 had no effect on drug extraction. Conclusions: R-IP combined with urea is expected to not only shorten the treatment time but also enable its application to drugs with low concentrations in blood. Full article

Background/Objectives: Extracellular vesicles (EVs) are nanoscale, membrane-enclosed structures that play key roles in intercellular communication and biological regulation. Among them, Lactobacillus paracasei-derived EVs (Lp-EVs) have attracted attention for their anti-inflammatory and anti-aging properties, making them promising candidates for therapeutic and cosmetic use. However, methods for specific detection and quantitative evaluation of Lp-EVs are still limited. This study aims to develop a surface plasmon resonance (SPR)-based sensor system for the precise and selective detection of Lp-EVs. Methods: Anti-p40 antibodies were immobilized on gold thin films to construct an SPR sensing platform. The overexpression of the p40 protein on Lp-EVs was confirmed using flow cytometry and Western blotting. For functional evaluation, Lp-EVs were applied to an artificial skin membrane mounted on a Franz diffusion cell, followed by SPR-based quantification and fluorescence imaging to assess their skin penetration behavior. Results: The developed SPR sensor demonstrated high specificity and a detection limit of 0.12 µg/mL, with a linear response range from 0.1 to 0.375 µg/mL. It successfully discriminated Lp-EVs from other bacterial EVs. In the skin diffusion assay, Lp-EVs accumulated predominantly in the epidermal layer without penetrating into the dermis, likely due to their negative surface charge and interaction with the hydrophobic epidermal lipid matrix. Fluorescence imaging confirmed this epidermal confinement, which increased over 24 h. Conclusions: This study presents a sensitive and selective SPR-based platform for detecting Lp-EVs and demonstrates their potential for targeted epidermal delivery. These findings support the use of Lp-EVs in skin-focused therapeutic and cosmetic applications. Future studies will explore strategies such as microneedle-assisted delivery to enhance transdermal penetration and efficacy. Full article

Skin infections are common in veterinary practice and are often treated with topical agents. Superficial pyoderma (superficial bacterial folliculitis) is a common cause of skin disease in dogs and a reason for treatment, most caused by Staphylococcus spp. strains. The frequent use of antibiotics contributes to the emergence of resistant bacterial strains, making antimicrobial resistance (AMR) one of the most important threats to human and animal health. For this reason, active natural compounds are increasingly being explored as alternative therapies. To contribute to the development of effective treatments for bacterial infectious diseases, researchers are looking for new antimicrobial agents. Topical drug action has many advantages as it avoids systemic reactions and ensures that the active substance reaches the site of the lesion directly. This study aimed to develop gelled dosage forms with propolis extract and to evaluate their antibacterial activity and the release of the active substances. Hydrogels, oleogels, and bigels enriched with eutectic propolis extract were produced. Deep eutectic solvents (DESs) were chosen as an effective tool to extract the active compounds of propolis and to improve their penetration into the skin. The pH values of the semi-solid pharmaceutical forms tested ranged from 3.3 to 6.4. Using modified Franz-type diffusion cells, the release of phenolic compounds from gels, oleogels, and bigels was assessed and quantified spectrophotometrically using the Folin–Ciocalteu method. The highest amount of active compounds was released from the hydrogels, while the lowest amount was released from the castor oil-based oleogel. The study used clinical and reference strains of bacteria. The antimicrobial activity of the gelled dosage forms with propolis extract was tested against six pathogenic bacterial species (S. aureus, S. agalactiae, B. cereus, E. faecalis, E. coli, Ps. aeruginosa) and one pathogenic fungus (C. albicans). The study’s results suggest that the propolis extract obtained by DES has significant antibacterial activity and is a promising component in skin formulations for the treatment of bacterial infections. Full article

Background/Objectives: Natural products are gaining increasing importance due to the large variety of biological activities exerted by their constituents. Among these, the products deriving from Acmella oleracea (L.) R.K. Jansen can be exploited for their local anaesthetic, myorelaxant, anti-inflammatory/analgesic, and antifungal properties. In this regard, there is a need to develop novel formulations for the topical delivery of A. oleracea-derived extracts to widen their use in the pharmaceutical and cosmetic fields. Methods: Nanoformulations, i.e., nanoemulsions (NEs) and microemulsions (MEs), were investigated as a strategy to encapsulate an extract from A. oleracea at the nanoscale level in water and then incorporated into xanthan gum-based hydrogels. Results: Only NEs provided a physically stable formulation, while the precipitation of solid hydrophobic components from the extract was observed during ME preparation under all tested conditions despite the use of ethyl oleate as an oily co-solvent. The optimized NE-based hydrogel remained physically stable over six months, as confirmed by rheological measurements and polarized optical microscope observation, without a phase separation phenomenon. Therefore, NEs resulted more suitable nanodispersed systems than MEs for the encapsulation of A. oleracea extract, which contains a large amount of hydrophobic constituents that are solid at room temperature. Furthermore, the sustained spilanthol release across an artificial membrane (Franz cell apparatus) and the cytotoxic profile on HaCaT cell line support its potential topical application. Conclusions: The outcomes of this study provided valuable insights into the formulation of A. oleracea extract, broadening its fields of applicability, including topical administration. Full article

Background: Trichophyton indotineae terbinafine-resistant infections are emerging in healthy individuals. Luliconazole, an imidazole antifungal that is effective against skin infections, faces challenges due to low water solubility and poor skin penetration. This study aimed to formulate a luliconazole-loaded nanostructured lipid-carrier (NLC) gel in a Carbopol-based system to enhance drug absorption and efficacy in a guinea pig model of dermatophytosis. Methods: Luliconazole-loaded nanostructured lipid carriers (NLCs) were prepared using a solvent evaporation method and gel formulation. Skin absorption and retention were assessed via Franz diffusion cells. The antifungal efficacy was tested against T. indotineae in thirty guinea pigs with induced tinea corporis, divided into five treatment groups. Mycological, clinical, and histopathological evaluations were conducted, along with skin irritation studies for safety. Results: LCZ-NLC demonstrated significantly better skin penetration than simple luliconazole gel, with cumulative drug penetration of 71.8 ± 3.7 μg/cm² versus 50.9 ± 4.2 μg/cm² after 24 h. Both formulations achieved complete infection resolution after 21 and 28 days, with reduced inflammation and no local irritations. On day 21, the LCZ-NLC 1% gel significantly reduced lesion scores and mycological evidence of infection compared to the terbinafine-treated groups, untreated controls, and NLC-gel-treated group (p < 0.05). Histopathological analysis indicated a reduction in both epidermal thickening and fungal burden in the models that received treatment with the LCZ-NLC 1% gel. Conclusions: Luliconazole-loaded lipid carriers enhance drug absorption and efficacy, suggesting shorter treatment durations and improved patient outcomes for resistant fungal infections. However, further studies are warranted to correlate these findings with clinical outcomes. Full article

Background: Various routes of drug administration are available for psoriasis treatment. However, there is an urgent need for novel and improved therapeutic options. Hence, our study aimed to develop a nanostructured lipid carrier (NLC) gel of hesperidin (HPD) using a systemic QbD approach for an effective treatment of psoriasis. Methods: Initially, HPD-NLC was optimized with independent variables (drug content, amount of liquid lipid, total lipid, and surfactant concentration) using Box–Behnken Design to assess dependent variables (particle size, size distribution, and entrapment efficiency). HPD-NLC was developed using the high-shear homogenization technique. The characteristics of nanoformulation such as particle size, morphology [transmission electron microscopy (TEM) and differential scanning calorimetry (DSC)], crystallinity [powder X-ray diffraction (XRD)], and chemical interactions [Fourier transform infrared spectroscopy (FTIR)], the drug entrapment efficiency (%EE), and the drug release were investigated. Franz-diffusion cell was utilized to perform in vitro diffusion study, and an imiquimod-induced psoriasis model was used for in vivo study. Results: The optimized HPD-NLC exhibited a spherical shape with particle size of 125.7 nm, polydispersity index (PDI) of 0.36, and entrapment efficiency of 52.26% w/w. Further, different techniques validated the reduced crystallinity of the hesperidin. The in vitro diffusion study highlighted the sustained and anomalous diffusion of the drug from NLC gel. In the in vivo study, the HPD-NLC-Gel-treated group displayed normal skin with minimal keratosis, while the drug-loaded gel group exhibited signs of hyperkeratosis and parakeratosis signs. Conclusions: HPD-NLC gel showed promising advancement in nanotechnology-based psoriasis treatment and the results of this study open the door for the application of topical HPD-NLC-Gel clinically. Full article