Search Results (85)

This review considers L-ascorbic acid as a test substance in designing a dermal drug delivery system for carrying a hydrophilic, low-stability API. Actual studies of nano delivery systems carrying L-ascorbic acid are reviewed. L-ascorbic acid and other antioxidant substances are present in the skin at high levels compared with blood plasma. Augmenting these L-ascorbic acid levels by topical administration may have benefit, but other antioxidants may also need to be augmented. Coadministration of other APIs with L-ascorbic acid may be beneficial, but synergetic interactions are rare and difficult to predict. Some studies reviewed used in vitro methods for quantifying skin retention of API in the living skin layers. These methods may be inadequate. In vivo mouse and rat models suggest therapeutic value of L-ascorbic acid in the skin, but since these animal skins are more permeable than human skin, evidence for good API retention in human skin is weak. Studies using inorganic or polymer nanoparticles for L-ascorbic acid include a lack information concerning skin permeability and retention. Liposome-like systems seem to be the main focus of research now. These studies challenge the understanding of skin penetration mechanisms. Predictions that positively charged deformable liposomes are superior to negatively charged non-deformable liposomes fail. Full article

Background/Objectives: Microneedling is increasingly applied to enhance transepidermal drug delivery. Calcium hydroxyapatite (CaHA) has recognized biostimulatory properties, but its delivery and distribution within the dermis remain poorly characterized. This study aimed to evaluate the efficacy of microneedling for transepidermal CaHA delivery, focusing on retention, dispersion, and collagen expression, and to investigate the role of hyaluronidase in modulating these effects. Methods: Fluorescently labeled CaHA nanopowder was characterized using scanning electron microscopy (SEM) and confocal fluorescence microscopy. Nine experimental groups were established, varying microneedling intensity and hyaluronidase application. Ex vivo porcine skin samples were analyzed histologically for CaHA penetration and distribution. HaCaT keratinocyte cultures were treated with CaHA, and mRNA expression of collagen types I, III, IV, and MMP-1 was quantified. Results: High-intensity microneedling improved CaHA retention but caused tissue damage. Low-intensity microneedling showed limited retention, enhanced by hyaluronidase co-application. In vitro, CaHA increased collagen type III and IV expression, while collagen type I and MMP-1 remained unchanged. Conclusions: Microneedling effectively delivers CaHA into the dermis and stimulates collagen remodeling. Optimizing microneedling intensity is essential to balance efficacy and safety, and hyaluronidase may enhance clinical outcomes by improving CaHA distribution. Full article

Background: Skin mycoses affect approximately 10% of the global population, and the range of effective topical antifungal agents remains limited. Voriconazole (VRC) is a broad-spectrum triazole with proven efficacy against drug-resistant fungal infections. This study aimed to develop and optimize VRC-loaded microemulsion (ME) polymer gels (Carbopol^®-based) for cutaneous delivery. Selected formulations also contained menthol (2%) as a penetration enhancer and potential synergistic antifungal agent. Methods: A comprehensive screening was performed using pseudoternary phase diagrams to identify stable oil/surfactant/co-surfactant/water systems. Selected MEs were prepared with triacetin, Etocas™ 35, and Transcutol^®, then gelled with Carbopol^®. Formulations were characterized for pH, droplet size, polydispersity index (PDI), and viscosity. In vitro VRC release was assessed using diffusion cells, while ex vivo permeation and skin deposition studies were conducted on full-thickness human skin. Rheological behavior (flow curves, yield stress) and texture (spreadability) were evaluated. Antifungal activity was tested against standard strain of Candida albicans and clinical isolates including a fluconazole-resistant strain. Results: The optimized ME (pH ≈ 5.2; droplet size ≈ 2.8 nm) was clear and stable with both VRC and menthol. Gelation produced non-Newtonian, shear-thinning hydrogels with low thixotropy, favorable for topical application. In ex vivo studies, performed with human skin, both VRC-loaded gels deposited the drug in the epidermis and dermis, with no detectable amounts in the receptor phase after 24 h, indicating retention within the skin. Menthol increased VRC deposition. Antifungal testing showed that VRC-containing gels produced large inhibition zones against C. albicans, including the resistant isolate. The VRC–menthol gel exhibited significantly greater inhibition zones than the VRC-only gel, confirming synergistic activity. Conclusions: ME-based hydrogels effectively delivered VRC into the skin. Menthol enhanced drug deposition and demonstrated synergistic antifungal activity with voriconazole. Full article

Purpose: This study was designed to develop a nanoparticle-based methotrexate (MTX) and sorafenib (SRF)-loaded transferosome (MTX-SRF-TFS) for effective management of arthritis through the transdermal route. Methods: For the preparation of MTX-SRF-TFS, the thin-film hydration technique was selected and optimized using Box–Behnken Design. The particle size of the nanoparticles was determined using a Malvern Zeta sizer and electron microscopy. An in vivo skin retention and penetration study was also conducted to evaluate the designed delivery system. Furthermore, the therapeutic response of MTX-SRF-TFS was determined using the CFA-induced mouse model. Results: The optimized MTX-SRF-TFS formulation (F4), having an average particle size (PS) of 162.20 ± 2.89 nm and percent entrapment efficiency (%EE) of MTX and SRF of 92.16 ± 4.95 and 81.54 ± 3.23, respectively, was selected for further assessment. Due to the deformable nature of MTX-SRF-TFS, MTX and SRF penetrate more deeply into the cutaneous layers, exhibiting an enhanced transdermal effect, as shown by the results of ex vivo skin permeation and retention studies. Furthermore, in vivo anti-arthritic studies have shown the superior pharmacodynamic response of MTX and SRF when incorporated into transferosomes, as it caused a marked reduction in arthritic score and paw diameter in CFA-induced arthritis in BALB/c mice. Histopathology analysis and X-ray radiography also confirmed the findings that MTX-SRF-TFS has improved anti-arthritic response in contrast to plain MTX-SRF gel. Conclusions: The MTX-SRF-TFS is highly effective in managing CFA-induced arthritis, and the designed delivery system should be further evaluated on pharmacokinetic grounds to progress towards clinical studies. Full article

Purpose: Androgenetic alopecia (AGA) is a common, chronic, non-cicatricial dermatological condition characterized by progressive miniaturization of hair follicles. Although AGA is a benign disorder, it has a considerable impact on patients’ quality of life and psychological health. The current treatment options often demonstrate limited efficacy and are frequently associated with undesirable side effects. This study aimed to co-mill two natural compounds, quercetin (QT) and glycyrrhizic acid (GL), to develop follicle-targeted nanocrystals (NCs), thereby enhancing local accumulation, improving the pathological follicular microenvironment associated with AGA, and promoting hair regrowth. Methods: QT nanocrystals (QT-NCs) were fabricated using a top–down wet media milling technique with GL as a bioactive stabilizer. The resulting QT-NCs were characterized regarding their particle size, crystallinity, morphology, and stability. The skin permeation properties of the QT-NCs were further evaluated in vitro, and their therapeutic efficacy was assessed in a dihydrotestosterone (DHT)-induced AGA mouse model. Results: The QT-NCs exhibited an irregular structure with a particle size ranging from 200 to 300 nm, demonstrating uniform dimensions and excellent storage stability. In vitro permeation studies revealed a 2.27-fold increase in cumulative penetration and a 2.47-fold enhancement in skin retention compared to raw QT. In the DHT-induced AGA mouse model, QT-NCs significantly reduced local DHT levels while concurrently modulating the follicular microenvironment, resulting in markedly improved therapeutic outcomes. Notably, when co-administered, QT and GL demonstrated synergistic pharmacological effects, suggesting potential combinatory benefits. Conclusions: This study presents the first demonstration of QT-NCs for AGA treatment, establishing a novel therapeutic strategy with substantial potential for clinical translation. Full article

Background: Skin injuries, such as chronic wounds and inflammatory skin diseases, often face limitations in treatment efficacy due to the low efficiency of transdermal drug delivery and insufficient local concentrations. Curcumin (CUR), a natural compound with anti-inflammatory and antioxidant properties, has demonstrated potential in the repair of skin damage; however, its clinical application is hindered by its physicochemical characteristics. This study constructs a novel nanocomposite drug delivery system: CUR-loaded micellar nanocomposite gel (CUR-M-DMNs-Gel). A composite system is used to achieve the efficient solubilization and enhanced transdermal permeation of CUR, thereby providing a novel formulation approach for the treatment of skin diseases. Methods: CUR-loaded micellar (CUR-M) utilizes CUR as the core active ingredient, which possesses multiple pharmacological effects including anti-inflammatory and antioxidant properties. TPGS serves as a micellar carrier that not only enhances the solubility and stability of CUR through its amphiphilic structure but also facilitates drug absorption and transport within the body. In dissolvable microneedles (DMNs), PVP K30 forms a stable three-dimensional network structure through entanglement of polymer chains, ensuring sufficient mechanical strength for effective penetration of the skin barrier. Meanwhile, PVP K90, with its higher molecular weight, enhances the backing’s support and toughness to prevent needle breakage during application. The incorporation of hyaluronic acid (HA) improves both the moisture retention and adhesion properties at the needle tips, ensuring gradual dissolution and release of loaded CUR-M within the skin. In CUR-loaded micellar gel (CUR-M-Gel), PVP K30 increases both adhesive and cohesive forces in the gel through chain entanglement and hydrogen-bonding interactions. Tartaric acid precisely regulates pH levels to adjust crosslinking density; glycerol provides a long-lasting moisturizing environment for the gel; aluminum chloride enhances mechanical stability and controlled drug-release capabilities; NP-700 optimizes dispersion characteristics and compatibility within the system. Results: In vitro experiments demonstrated that the CUR-M-DMNs-Gel composite system exhibited enhanced transdermal penetration, with a cumulative transdermal efficiency significantly surpassing that of single-component formulations. In the mouse skin defect model, CUR-M-DMNs-Gel facilitated collagen deposition and effectively inhibited the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β). In the mouse skin photoaging model, CUR-M-DMNs-Gel markedly reduced dermal thickness, alleviated damage to elastic fibers, and suppressed inflammatory responses. Conclusions: The CUR-M-DMNs-Gel system can enhance wound healing through subcutaneous localization, achieving long-term sustained efficacy. This innovative approach offers new insights into the treatment of skin injuries. Full article

Equisetum telmateia Ehrh. (great horsetail) belongs to the Equisetaceae family and its aerial parts have been traditionally used for skin conditions and to achieve healthy and resilient skin, nails, and hair. This study aimed to evaluate the inhibition of skin-related enzymes by, the antioxidant capacity of, and the phytochemical composition of E. telmateia. Additionally, a novel emulgel was formulated from the main methanolic extract and characterized in terms of pH, viscosity, determination of content quantification, textural profile analysis, and spreadability. After the characterization studies, in vitro release and ex vivo permeation and penetration studies were performed. Firstly, the dried aerial parts of E. telmateia were macerated in methanol, followed by partitioning with solvents of increasing polarity: n-hexane, chloroform, ethyl acetate, and n-butanol. Antioxidant activity was assessed using DPPH, FRAP, CUPRAC, and TOAC assays, while enzyme inhibition was analyzed for collagenase, elastase, hyaluronidase, and tyrosinase. LC-MS/MS analysis identified 53 phytochemical compounds. Protocatechuic acid, the main phenolic compound, was quantitatively analyzed in each subfraction by HPTLC. The in vitro release studies showed sustained release of the reference substance (protocatechuic acid) and the kinetic modeling of the release was fitted to the Higuchi model. The ex vivo permeation and penetration studies showed that the formulation exhibited a retention of 3.06 ± 0.21 µg.cm⁻² after 24 h, whereas the suspended extract demonstrated a skin retention of 1.28 ± 0.47 µg.cm⁻². Both the extracts and the formulated emulgel exhibited inhibitory effects on skin-related enzymes. Our finding suggested that E. telmateia might be a valuable ingredient for wrinkle care and skin-regenerating cosmetics. Full article

Objectives: Sialic acid (SA), a naturally occurring compound abundantly found in birds’ nests, holds immense promise for skincare applications owing to its remarkable biological properties. However, its low bioavailability, poor stability, and limited skin permeability have constrained its widespread application. Methods: To overcome these challenges, SA was encapsulated within nanoliposomes (NLPs) by the high-pressure homogenization technique to develop an advanced and efficient transdermal drug delivery system. The skincare capabilities of this novel system were comprehensively evaluated across multiple experimental platforms, including in vitro cell assays, 3D skin models, in vivo zebrafish studies, and clinical human trials. Results: The SA-loaded NLPs (SA-NLPs) substantially improved the transdermal penetration and retention of SA, facilitating enhanced cellular uptake and cell proliferation. Compared to free SA, SA-NLPs demonstrated a 246.98% increase in skin retention and 1.8-fold greater cellular uptake in HDF cells. Moreover, SA-NLPs protected cells from oxidative stress-induced damage, stimulated collagen synthesis, and effectively suppressed the secretion of matrix metalloproteinases, tyrosinase activity, and melanin production. Additionally, zebrafish-based assays provided in vivo evidence of the skincare efficacy of SA-NLPs. Notably, clinical evaluations demonstrated that a 56-day application of the SA-NLPs-containing cream resulted in a 4.20% increase in L*, 7.87% decrease in b*, 8.45% decrease in TEWL, and 4.01% reduction in wrinkle length, indicating its superior brightening, barrier-repair, and anti-aging effects. Conclusions: This multi-level, systematic investigation strongly suggests that SA-NLPs represent a highly promising transdermal delivery strategy, capable of significantly enhancing the anti-aging, barrier-repair, and skin-brightening properties of SA, thus opening new avenues for its application in the fields of dermatology and cosmeceuticals. 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

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

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: 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: Alopecia areata is an autoimmune disorder that causes hair loss in clumps about the size and shape of a quarter. The estimated prevalence of the disorder is approximately 1 in 1000 people, with a lifetime risk of approximately 2 percent. One of the systemic therapies for alopecia areata consists of the use of glucocorticoids or immunosuppressants. Methods: Baricitinib (BCT) is a Janus kinase (JAK) 1 and 2 selective inhibitor used as an immunosuppressant drug. In this study, three olive oil BCT formulations (Oil A, Oil B, and Oil C, which differ in their content in squalene, tocopherol, tyrosol, and hydroxytyrosol) have been developed for topical delivery. The formulations were physicochemically characterized and the in vitro drug release and ex vivo permeation through human skin tissues were assessed. Results: The results showed nearly identical viscosity across all three formulations, exhibiting Newtonian behavior. The mathematical modeling used to describe the drug release profiles was the one-site binding hyperbola for all formulations. Oil-based formulations showed a slow BCT penetration into human skin. Skin integrity remained intact during the experiments, with no signs of irritation or alterations observed. In addition, all the formulations proved their efficacy in vivo. Conclusions: Among the formulations, Oil A demonstrated the highest ability retention capacity (Q_r = 1875 ± 124.32 ng/cm²) in the skin, making it an excellent candidate for further investigation in the treatment of alopecia areata. Full article

Background: Rutin is a natural flavonoid extracted primarily from plants with anti-inflammatory and antioxidant properties, and it is highly valuable in the cosmetics industry. However, the poor transdermal permeability of rutin limits its application via transdermal administration. Previous studies have predominantly focused on chemical methods for enhancing penetration. This study investigated the potential of ultrasound as a physical method by which to augment the transdermal absorption and anti-inflammatory effects of rutin. Method: Through in vitro diffusion experiments, we analyzed the effects of the ultrasonic frequency and intensity on percutaneous absorption. The optimal ultrasound parameters were determined based on the intradermal retention rate, which is defined as the proportion of intradermal retention to the total penetration. Parameters with higher retention rates were considered optimal. To validate the anti-inflammatory efficacy of rutin delivered using the ultrasound-assisted method, we employed a tape-stripping technique to induce inflammation in BALB/c nude mice. Eight mice were assigned to each treatment group: (A) self-repair (control group), (B) regular rutin treatment, and (C) ultrasound-assisted treatment. Results: The research findings indicate that ultrasound frequency and intensity of 1 MHz and 0.2 W/cm², as well as 3 MHz and 0.2 W/cm², result in the maximum proportion of rutin intradermal retention, exhibiting values 1.8 times (using porcine skin) and 2.63 times (using nude mouse skin) higher than those achieved without ultrasound, respectively. Group C showed the shortest recovery time and displayed complete skin barrier function restoration by the fourth day $(p<0.05)$, whereas group A exhibited the slowest recovery. Conclusions: This study offers an innovative approach for the transdermal delivery of rutin to facilitate skin barrier function repair. Full article

Hydrogel microneedles (HMNs) have emerged as a transformative platform for minimally invasive drug delivery and biosensing, offering enhanced bioavailability, controlled drug release, and real-time biomarker detection. By leveraging swelling hydrogels, nanomaterial integration, and stimuli-responsive properties, HMNs provide precision medicine capabilities across diverse therapeutic and diagnostic applications. However, challenges remain in mechanical stability, as hydrogel-based MNs must balance flexibility with sufficient strength for skin penetration. Drug retention and controlled release require optimization to prevent premature diffusion and ensure sustained therapeutic effects. Additionally, biosensing accuracy is influenced by variability in interstitial fluid extraction and signal transduction. Clinical translation is hindered by regulatory hurdles, scalability concerns, and the need for extensive safety validation in human trials. This review critically examines the key materials, fabrication techniques, functional properties, and testing frameworks of HMNs while addressing these limitations. Furthermore, we explore future research directions in smart wearable MNs, AI-assisted biosensing, and hybrid drug–device platforms to optimize transdermal medicine. Overcoming these barriers will drive the clinical adoption of HMNs, paving the way for next-generation patient-centered therapeutics and diagnostics. Full article