Skin absorption and metabolism of a new vitamin E prodrug, delta-tocopherol-glucoside: in vitro evaluation in human skin models.
The aim of this study was to investigate the cutaneous penetration and metabolism of the new vitamin E prodrug delta-tocopherol glucoside (delta-TG), as compared to those of common vitamin E acetate, in vitro, both in reconstituted human epidermis and in viable human skin. Better diffusion was observed with alpha-tocopherol acetate (alpha-TAc) than with delta-tocopherol glucoside in both skin models, at 0.1% and 0.05% in a myritol solution; however, no metabolism was detected with alpha-tocopherol acetate. In all conditions tested (two skin models, two concentrations, three test times, and compartmental analysis) the delta-tocopherol glucoside was metabolized into free tocopherol. In the reconstituted human epidermis, after 18 h, over 90% of the delta-tocopherol glucoside was bioconverted. In the viable human skin, the extent of metabolism was about 20%, with 0.12 and 0.10 microg/cm2 of delta-tocopherol glucoside in the stratum corneum and epidermis, respectively. After topical application, the delta-tocopherol glucoside had a considerable reservoir effect, associated with gradual delivery of free tocopherol. The use of this gluco-conjugated vitamin E at a low concentration shows the capability of the skin to metabolize the prodrug in a slow and prolonged manner, making this gluco-conjugated vitamin E an excellent candidate for continuous reinforcement of antioxidants in the skin.
Mavon
Alain
A
Laboratoire de Pharmacocinétique Cutanée, Institut de Recherche Pierre Fabre, 31320 Vigoulet-Auzil, France. alain.mavon@pierre-fabre.com
Raufast
Véronique
V
Redoulès
Daniel
D
D000975:Antioxidants / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D020405:Dermis / Q000737:chemistry / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism; D005960:Glucosides / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D011355:Prodrugs / Q000493:pharmacokinetics*; D012867:Skin / Q000737:chemistry / Q000378:metabolism; D012869:Skin Absorption; D024505:Tocopherols / Q000493:pharmacokinetics*; D014810:Vitamin E / Q000493:pharmacokinetics*
D000975:Antioxidants; D003692:Delayed-Action Preparations; D005960:Glucosides; D011355:Prodrugs; C497814:delta-tocopherol glucoside; D014810:Vitamin E; D024505:Tocopherols