In Vitro Assessment of the Tolerance Profile, the Metabolism and the Potential Depigmenting Activity of New Retinoid Derivatives

Abstract

Abstract:Background: In spite of the numerous depigmenting agents available, there is an inverse relationship between safety and efficiency. Natural retinoids exert depigmenting activities in vivo, but have a narrow therapeutic window. There is thus a need for a new class of depigmenting agents that would be both safe and useful.Objective: The aim of the study was to analyse the potential interest of new retinoid derivatives as topical depigmenting agents. Methods:The tolerance profile of the new retinoids was analysed in murine BDVII keratinocytes and murine B16 melanocytes using the MTT assay. The uptake and the metabolism of the retinoids were analysed in keratinocytes and melanocytes by HPLC/UV. The cellular content of melanin was determined in melanocytes using a photometric assay.Results: Methyl-and t-butyl-4-oxoretinoate, arbutin retinoate and retinoic acid were shown to have the best depigmenting potential according to the ratio between the IC 50 for MTT assay and that for melanin content. Retinaldehyde, 4-hydroxyretinaldehyde and methyl-4-hydroxyretinoate have a good depigmenting potential too, although the therapeutic window is narrower due to a higher toxicity.Conclusion: 4-Oxoesters of retinoic acid, arbutin retinoate and 4-hydroxyretinaldehyde derivatives offer a new family of depigmenting agents acting via a different pathway than tyrosinase inhibitors.