27742 From the inside-out: A more effective way of delivering ceramides to the stratum corneum – an in silico simulation study

A conventional approach to supplying stratum corneum (SC) lipids is through direct topical application of SC lipid-containing formulations. The effectiveness of this “outside-in” approach is subject to the dermal delivery potential of lipids. Topically applied ceramides have been reported to remain at the skin surface with little permeation. Short-chain fatty acids, however, may be delivered to the viable epidermis (VE) where they can be converted into longer-chain fatty acids and ceramides via metabolism, potentially providing an “inside-out” approach for SC lipid replenishment. The objective of this research was to assess, via in silico simulation, whether large SC lipid species are better delivered into the skin using the “inside-out” or “outside-in” approach. The dermal delivery of fatty acids, cholesterol and ceramides from single and repeated topical dosing were simulated using a previously published, validated mathematical model. The predicted levels and depth profiles were analyzed to assess the effectiveness of lipid replenishment approaches. Short-chain fatty acids were predicted to have the highest dermal delivery potential, while ceramides have the lowest. The predicted delivery of fatty acids was ∼5x and several orders higher than that of ceramides in the SC and in the VE, respectively. With repeated topical dosing, sufficient amount of short-chain fatty acids were predicted to be delivered to the VE for metabolism, while ceramides were mostly retained at the skin surface. The results here suggested that applying short-chain fatty acids topically, which are converted into ceramides, is a more effective approach for delivery of ceramides into the SC.