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Ascorbic acid (AA) is a water-soluble vitamin that is found at high concentrations in normal skin. The important and well-known benefits of using AA in skin health include the stimulation of collagen synthesis and the assistance of protection against photo-oxidative damages. To maintain stability and improve drug delivery to the active site, a variety of AA derivatives have been chemically synthesized. Among these compounds, we focus here on a lipophilic derivative, 3-O-cetyl ascorbic acid (3-CetylAA), which remains poorly characterized for cosmetic applications. Uptake analysis in three healthy human volunteers’ skin was conducted using a serial tape-stripping technique detecting 3-CetylAA (on average, 128 ± 27 pmol per µg) in the stratum corneum after a 5-h topical treatment when treated with 25 mM 3-CetylAA-containing cream for 13 days twice daily and continuously. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging of vertical cryosections of pig skin revealed the presence of 3-CetylAA in the epidermal layer after topical treatment with 3-CetylAA-containing cream. In sun-exposed human skin, 3-CetylAA improved the texture after treatment with 25 mM 3-CetylAA-containing cream for 4 weeks or more when used twice daily or continuously. An in vitro transformation assay using BALB/c 3T3 A31-1-1 cells demonstrated that 10 µM 3-CetylAA, which is the same concentration exhibited in vitro biological activities in another lipophilic AA derivative, 2-O-octadecyl ascorbic acid, was non-carcinogenic and did not potentiate the UVC-induced transformation frequency when applied for 3 days after UVC irradiation. These results demonstrate that 3-CetylAA is a promising candidate as a lipophilic derivative of AA for cosmetic purposes.

Facial Treatment with 3-O-Cetyl Ascorbic Acid for Improvement of Skin Texture: Uptake, Effectiveness, and In Vitro Carcinogenicity Assessment