title: Synthesis, hydrolysis, and skin retention of amino acid esters of alpha-tocopherol.
abstract: The aim of this work was to synthesize new pro-vitamins of alpha-tocopherol (VE) able to release another moiety such as an amino acid, in order to obtain a combined antioxidant and moisturizing effect upon topical application. The new derivatives were characterized and tested for sensitivity to chemical and enzymatic hydrolysis. Lipophilicity was estimated using Log capacity factor and skin retention was determined in vitro, using rabbit ear skin as barrier. Five molecules were synthesized using L-proline, L-serine, L-tyrosine, L-asparagine, and L-citrulline as amino acidic moiety. All pro-vitamins showed similar or lower lipophilicity than alpha-tocopheryl acetate (VEAc), taken as reference, and similar stability in aqueous solutions. All pro-vitamins showed to be sensitive to enzymatic hydrolysis. None of the pro-vitamins crossed the skin in significant amounts, whereas they accumulated into the skin, in both the dermis and the epidermis. They are more hydrophilic and more water-soluble than the currently used acetate.
authors.affiliation: Dipartimento Farmaceutico, University of Parma, Viale G.P. Usberti 27/A, 43100 Parma, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Marra
authors.forename: Carmine
authors.initials: C
authors.lastname: Ostacolo
authors.forename: Sonia
authors.initials: S
authors.lastname: Laneri
authors.forename: Antonietta
authors.initials: A
authors.lastname: Bernardi
authors.forename: Antonia
authors.initials: A
authors.lastname: Sacchi
authors.forename: Cristina
authors.initials: C
authors.lastname: Padula
authors.forename: Sara
authors.initials: S
authors.lastname: Nicoli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Santi
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D004950:Esterases / Q000378:metabolism; D006868:Hydrolysis; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000201:enzymology; D011817:Rabbits; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012995:Solubility; D013552:Swine; D014810:Vitamin E / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D008055:Lipids; D014810:Vitamin E; D004950:Esterases; D024502:alpha-Tocopherol