Drug delivery system (DDS)-inspired cosmetic liposomes: Unveiling physicochemical determinants of skin penetration under practical application conditions.

Although liposomes are widely studied in pharmaceutical drug delivery systems (DDS), their penetration behavior under practical cosmetic application conditions remains poorly understood. To establish design guidelines based on DDS concepts, this study elucidated how the physicochemical properties of cosmetic liposomes govern human skin penetration. Five types of liposomes were prepared with systematically varied particle sizes, membrane fluidities, and surface charges using a modified polyol dilution method. Skin penetration evaluation using excised human skin revealed distinct trends relative to the standard sample. The results showed that larger-sized liposomes exhibited gradual penetration, delaying initial delivery (0.7-fold relative to the standard sample at 2 h). High-membrane-fluidity liposomes enhanced penetration, rapidly increasing delivery in the stratum corneum (>6-fold relative to the standard sample at 2 h). Furthermore, positively charged cationic liposomes showed initial surface retention for up to 6 h, followed by enhanced penetration into deeper viable layers (2.4-fold relative to the standard sample at 24 h). Finally, liposomes combining high membrane fluidity and cationic charge exhibited synergistically enhanced skin penetration and retention. These results provide practical formulation guidelines for tuning cosmetic liposome performance.