Function and mechanism of hydrophilic drug-penetration enhancement using ultra-fine water particles on treated skin

The stratum corneum (SC), the outermost layer of the skin, serves as a significant barrier to transdermal drug delivery; therefore, effective penetration enhancers are critical for therapeutic applications. Ultra-fine water (UFW), a humidifier capable of generating nanometer-sized fine water particles, can improve skin barrier function, increase facial skin hydration, and enhance skin softness. However, its mechanism of action on the skin is not clear. Therefore, we aimed to clarify the effects of UFW on skin hydration and its penetration-enhancing properties for hydrophilic drug, particularly L-ascorbic acid 2-glucoside (AAG), and to investigate its mechanisms of action. In vitro studies demonstrated that UFW was rapidly absorbed into the SC, which maintained a higher water content than vapor-treated skin. AAG penetration studies revealed a mountainous flux profile with a peak at 15 min of UFW treatment, which significantly enhanced flux compared to that of untreated controls. A bilayer skin model was employed to calculate penetration parameters, diffusion coefficient and partition coefficient, in each layer, showing that UFW increased solubility in the SC and diffusivity in the viable skin (VS). Furthermore, extraction experiments confirmed that UFW facilitated the retention of AAG in the SC during the early stages of penetration and sustained its release over time. These findings suggest that UFW effectively enhances skin hydration and penetration of hydrophilic drugs, offering a safe and multifunctional tool for cosmetic and medical applications. Its unique properties make it a promising candidate for addressing challenges in transdermal drug delivery and skin treatment. • UFW rapidly absorbed into SC, with higher water content and lower TEWL than in vapor-treated skin • AAG penetration studies revealed mountainous flux profile with peak at 15 min • UFW increased solubility in the SC and diffusivity in the viable skin • UFW facilitated AAG retention in SC during early penetration and sustained release • UFW effectively enhances skin hydration and penetration of hydrophilic drug