Search Results (149)

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

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

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

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. 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

As the proportion of the elderly population increases, there is an urgent need for anti-aging technologies. Since the skin is the most visibly aging organ in the human body, it is crucial to develop active ingredients to slow down skin aging. Currently, identified anti-aging active substances include antioxidants, retinoids, peptides, growth factors, and compounds derived from biofermentation. However, they have limitations such as poor stability, low transdermal permeability, skin irritation, high effective concentrations, slow onset of efficacy, single-action mechanisms, and high production costs. These limitations highlight the necessity of developing new anti-aging technologies that are multifunctional and cause low irritation. This study aimed to investigate the anti-aging effects and mechanisms of fructosazine (FZ) and deoxyfructosazine (DOF) on the skin as well as their potential applications in skincare. The methods included ELISA tests to assess the viability of human dermal fibroblast (NHDF) cells and related factors, and monitoring in Sprague-Dawley (SD) rats. The results showed that FZ promoted cell viability. Both FZ and DOF enhanced the secretion of type I collagen (Col I) and hyaluronic acid (HA), inhibited matrix metalloproteinase-1 (MMP-1), boosted catalase (CAT), and reduced malondialdehyde (MDA), reactive oxygen species (ROS), and β-galactosidase. They also nourished the epidermis and increased fiber content. In conclusion, FZ and DOF can stimulate the production of anti-aging substances, exhibit antioxidant activity, and have potential in skincare. 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

Port-wine stain (PWS), a progressive congenital vascular malformation characterized by ectatic dermal capillaries, demonstrates age-dependent lesion expansion and chromatic intensification, resulting in significant psychosocial comorbidity. While systemic hematoporphyrin (HP) administration remains the clinical paradigm for photodynamic therapy (PDT), its therapeutic utility is severely constrained by non-targeted biodistribution. Pharmacokinetic analyses reveal prolonged dermal retention and suboptimal lesion accumulation, predisposing 42% of patients to phototoxic reactions. To address these limitations, this work creatively suggested a local targeted drug delivery method based on soluble microneedles in response to the difficulties mentioned above. The rational design of a molecular weight (MW) HA gradient system enabled the engineering of ternary nanocomposite microneedles with enhanced biomechanical integrity (0.49 N/needle) and superior HP loading capacity, which collectively facilitated spatiotemporally controlled transdermal delivery of hematoporphyrin with complete dissolution within 30 min. The release performance, skin permeability, and storage stability of hematoporphyrin dissolving microneedles (HP-DMNs) have all been demonstrated in vitro. This study applies soluble microneedle technology to the delivery of HP in PWS for the first time. It avoids the risk of systemic exposure through precise local administration. It uses the rapid dissolution properties of microneedles to achieve high concentration and rapid release of drugs in skin lesions. This study provides a new strategy for sustained intralesional release and rapid drug delivery treatment of PWS and provides novel ideas for the development of new formulations of HP and related photosensitizers. Full article

Transdermal drug delivery systems (TDDSs) provide a non-invasive alternative to oral and parenteral routes, delivering drugs into the bloodstream while avoiding gastrointestinal degradation and first-pass metabolism. Despite benefits like enhanced bioavailability and patient compliance, the stratum corneum limits drug permeation. Ethosomes overcome the stratum corneum barrier with superior flexibility and permeability compared to liposomes. Ethanol disrupts the skin’s lipid bilayer, enabling deep penetration and efficient drug delivery. Ethosomes offer high entrapment efficiency and stability, delivering both hydrophilic and lipophilic drugs. However, challenges like stability optimization and clinical translation persist. This review examines the structural components, preparation methods, and therapeutic applications of ethosomes in metabolic and chronic diseases, including diabetes, cardiovascular diseases, neurodegenerative disorders, arthritis, and cancers. Moreover, it highlights the potential of ethosomes to revolutionize TDDSs for managing chronic and metabolic diseases, providing a foundation for further research and clinical development. Full article

External environmental stressors and internal physiological changes frequently compromise the skin barrier, resulting in conditions such as dermatitis and dehydration. A key underlying factor is the depletion of ceramides, essential lipids in the stratum corneum that maintain skin integrity. Although topical ceramide supplementation is effective for barrier repair, its clinical application is limited by poor solubility and low skin permeability. To overcome these challenges, this study developed an oil-in-water nanoemulsion (O/W-NE) using ultrasonic emulsification for the efficient transdermal delivery of ceramide C2. Octyldodecanol was selected as the oil phase to enhance ceramide solubility, while glycerin was incorporated to increase aqueous phase viscosity, reduce particle size, and function as a biocompatible penetration enhancer. The optimized nanoemulsion achieved a particle size of 112.5 nm and an encapsulation efficiency of 85%. Its performance was evaluated via in vitro release, ex vivo skin permeation, and in vivo biocompatibility studies. Mechanistic investigations revealed that both particle size and glycerin concentration significantly influenced ceramide penetration into the epidermis and dermis. Additionally, the nanoemulsion exhibited moisturizing and barrier-repair effects in a damaged skin model. Overall, this O/W-NE offers a stable, non-invasive strategy for enhancing ceramide delivery and restoring skin barrier function. Full article

Background: We previously reported that carbopol hydrogels incorporating indomethacin nanoparticles (IMC NPs) improved the low permeability and bioavailability of skin formulations in transdermal drug delivery systems. However, the combination of NPs with other types of hydrogels has not been sufficiently explored to date. Therefore, this study investigated propylene glycol (PG)/polyvinyl alcohol (PVA) hydrogel as an alternative base to carbopol hydrogel for incorporating IMC NPs. Methods: IMC NPs were prepared using bead milling treatment, and these NPs were incorporated into PG/PVA hydrogel (IMC-NP@PG/PVA hydrogel). The IMC concentration was measured using the HPLC method, and seven-week-old Wistar rats were used to evaluate skin absorption. Results: Bead milling reduced the IMC particle size in the PG/PVA hydrogels to the nanoscale (30–200 nm) without altering its crystalline form. The IMC-NP@PG/PVA hydrogel exhibited enhanced uniformity, solubility, and drug release compared to the IMC microparticle-loaded PG/PVA hydrogel (IMC-MP@PG/PVA hydrogel), with a 1.44-fold greater area under the concentration–time curve. Transdermal permeability studies revealed that IMC-NP@PG/PVA had 2.36-fold higher absorption than the IMC-MP@PG/PVA hydrogel, with dissolved IMC permeating the skin. Pharmacokinetics in the rats showed significantly increased plasma levels, absorption rates, and bioavailability for IMC-NP@PG/PVA, demonstrating its superior delivery efficiency. Moreover, the skin absorption of IMC-NP@PG/PVA was higher than that of carbopol hydrogel. Conclusions: These findings highlight the potential of PG/PVA hydrogels as an effective base for transdermal drug delivery systems based on NPs. 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

The use of topical and transdermal drug delivery systems for nonsteroidal anti-inflammatory drugs (NSAIDs) has transformed pain management, inflammation, and skin conditions. This analysis highlights the topical and transdermal applications of ibuprofen, ketoprofen, and flurbiprofen, highlighting their excellent skin permeability and localized pain relief, as well as an evaluation of their safety in such applications. Their compatibility with diverse formulations, minimal systemic side effects, and widespread use in commercial products makes them ideal candidates for skin research and targeted therapy. Advances in transdermal delivery processes, such as the use of chemical enhancers, Solid Lipid Nanoparticles, vesicular systems, and hydrogels, have enhanced NSAID penetration and bioavailability. Physical techniques like iontophoresis and sonophoresis further enhance the transport of drugs across the stratum corneum of the skin. These approaches and processes enable more efficient and localized treatment of inflammatory conditions. The review emphasizes the need for continued innovation, interdisciplinary processes, and collaboration to overcome existing challenges. Future developments in nanotechnology and advanced drug delivery systems have the capability to enhance the effectiveness and safety of NSAIDs, paving the way for novel therapeutic solutions in managing pain and inflammation. Full article

Transdermal drug delivery systems (TDDS) offer an alternative to conventional oral and injectable drug administration by bypassing the gastrointestinal tract and liver metabolism, improving bioavailability, and minimizing systemic side effects. However, widespread adoption of TDDS is limited by challenges such as the skin’s permeability barrier, particularly the stratum corneum, and the need for optimized formulations. Factors like skin type, hydration levels, and age further complicate the development of universally effective solutions. Advances in artificial intelligence (AI) address these challenges through predictive modeling and personalized medicine approaches. Machine learning models trained on extensive molecular datasets predict skin permeability and accelerate the selection of suitable drug candidates. AI-driven algorithms optimize formulations, including penetration enhancers and advanced delivery technologies like microneedles and liposomes, while ensuring safety and efficacy. Personalized TDDS design tailors drug delivery to individual patient profiles, enhancing therapeutic precision. Innovative systems, such as sensor-integrated patches, dynamically adjust drug release based on real-time feedback, ensuring optimal outcomes. AI also streamlines the pharmaceutical process, from disease diagnosis to the prediction of drug distribution in skin layers, enabling efficient formulation development. This review highlights AI’s transformative role in TDDS, including applications of models such as Deep Neural Networks (DNN), Artificial Neural Networks (ANN), BioSIM, COMSOL, K-Nearest Neighbors (KNN), and Set Covering Machine (SVM). These technologies revolutionize TDDS for both skin and non-skin diseases, demonstrating AI’s potential to overcome existing barriers and improve patient care through innovative drug delivery solutions. Full article

Arnica montana (AM), which belongs to the daisy family Asteraceae, has a longstanding traditional use in Europe and North America for pain and inflammation treatment. This study investigates the inhibitory effects of ‘Arnica montana extract hydrogel patch (AHP)’ on Carrageenan-induced paw edema and hot plate-induced pain models. AHP exhibited transdermal permeability without the occurrence of issues like crystal precipitation. This study employed two animal model assessments using AHP, in comparison with Arnicare Gel (AG), to evaluate anti-inflammatory and pain relief effects. AHP treatment for 2 days showed a decrease in paw edema thickness in mice as compared to vehicle or AG groups; Carrageenan-induced swelling increased maximally at 1 h with the AHP group demonstrating a higher reduction. Thus, the AHP group exhibited a lower ratio of right/left paw thickness and a superior reduction in swelling, supportive of its ability to diminish edema. A histological analysis showed that AHP treatment reduced inflammatory cell infiltration. Consistently, the mRNA levels of inflammatory markers (tnfa, il1b, and il6) were decreased to a greater extent than the AG group. Particularly, tnfa inhibition was better in the AHP group, and the levels of il1b and il6 transcripts showed ~80% and 40% lower. Likewise, AHP reduced pain scores in a hot plate-induced rat model, although AG failed to do so. Together, these results demonstrate that AHP has long-lasting inhibitory effects on fluid effusion and edema formation, the production of inflammatory mediators, and pain-sensation, supporting its anti-inflammatory and pain-relieving pharmacological effects. Full article