Folate bioavailability in reconstructed skin models and effects of folate in a monolayer wound healing assay. Approaches on topic application

In chronic and degenerative diseases impacting the skin folates play an important metabolic role improving wound healing and reducing skin irritations. In contrast to systemic folate administration little is known on skin penetration of folates after topical application. Here the penetration of simple aqueous solutions of reduced folates have been investigated with in-vitro reconstructed skin models mimicking the barrier of native human skin. For up to 24 h, penetration of the epidermis by newly developed folate salts and formulations were investigated. Aqueous and lipophilic solutions of L-formyltetrahydrofolate and L-mefolinate salts were able to penetrate the epidermis. Even more importantly, the skin model revealed the metabolic conversion of L-folinate to L-methyltetrahydrofolate. Exemplarily the effects of these new folate salts have been tested on wound healing in a scratch assay with primary human keratinocytes. All folates applied were able to enhance wound healing compared to the control. Bioavailability, metabolic conversion and physiologic effectiveness of new folate formulation have been shown successfully in in vitro applications providing evidence for the potent applicability of the new folates in preparations for topic application.