Permeation behaviour of cosmetic actives into the human stratum corneum

Characterising the permeation of cosmetic actives through human skin is important for understanding their functional performance. Vitamin C derivatives, including 3-O-ethyl ascorbic acid and ascorbyl glucoside, are widely incorporated into skincare formulations for their antioxidant properties, while peptides such as palmitoyl tripeptide-1 (Pal-GHK) and palmitoyl tetrapeptide-7 (Pal-GQPR), present in Matrixyl™ 3000, are employed to promote extracellular matrix remodelling and reduce visible signs of skin ageing. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) and Orbital trapping SIMS (OrbiSIMS) were used to investigate the in vivo permeation behaviour of these cosmetic actives through the stratum corneum of three healthy female volunteers following topical application of cosmetic serum formulations. Serum formulations containing 3-O-ethyl ascorbic acid and Matrixyl™ 3000 were applied for exposure times of 0.5, 2, and 5 h, while a serum containing ascorbyl glucoside was applied for 0.5 h. Tape stripping of skin combined with SIMS analysis enabled an evaluation of both depth and lateral spatial distributions. For 3-O-ethyl ascorbic acid, the ascorbic acid fragment ion generated during SIMS analysis was used as a permeation marker due to its enhanced ionisation efficiency. A consistent decrease in signal intensity with stratum corneum depth was observed at all exposure times, indicating higher localisation at the surface of the stratum corneum. ToF-SIMS imaging further revealed heterogeneous lateral localisation of ascorbic acid throughout the stratum corneum, decorating corneocyte boundaries. ToF-SIMS depth profiling of ascorbyl glucoside revealed depth-dependent behaviour consistent with partitioning into intracellular regions of the stratum corneum. OrbiSIMS analysis of Pal-GHK and Pal-GQPR detected both peptides throughout every layer of the stratum corneum, demonstrating decreasing ion intensities with depth and no significant changes relative to exposure time. The OrbiSIMS depth profiling demonstrated that the ion intensities for both peptides dropped immediately, suggesting that they were only present on the outer surfaces of the cells and not within them (intercellular). Overall, these findings demonstrated that commonly used predictors such as lipophilicity do not fully determine permeation pathway selection within the stratum corneum and that SIMS-based techniques provide unique mechanistic insight into the spatial distribution and transport routes of cosmetic actives within human skin which will assist in the development of future products.