Transfersomes improved delivery of ascorbic palmitate into the viable epidermis for enhanced treatment of melasma.

ABSTRACT

Ascorbic palmitate (AP) is widely used in the topical pharmaceutical or cosmetic formulations for melasma treatment. However, the presence of the skin barriers makes it difficult for the highly lipophilic drug molecules to traverse the stratum corneum (SC) and diffuse into the viable epidermis (EP) to reach the melanocytes, thereby exerting suboptimal antimelasma effects. Herein, AP was encapsulated into the transfersomes (TFs), yielding AP-TFs. AP-TFs utilized the deformability of TFs to squeeze through the skin pores in the SC under the transepidermal hydration gradient forces, leading to 14.1-fold increase in AP accumulation to the EP. AP-TFs could slowly release the encapsulated AP, while whether the released AP or transfersomal AP showed comparable uptake into the melanocytes, thereby exerting similar inhibitory effects on tyrosinase activity and melanogenesis. Ultimately, in the rat melasma model, AP-TFs showed superior antimelasma efficacy to free AP, with effective relief of oxidative stress and inflammation in the skin. Moreover, AP-TFs did not induce skin irritation. Therefore, the study provides a safe and effective approach to elevating the delivery of highly lipophilic drugs to the EP for enhanced treatment of melasma.