title: Use of alpha-tocopherol esters for topical vitamin E treatment: evaluation of their skin permeation and metabolism.
abstract: OBJECTIVE
  The aim of this work was to investigate new pro-vitamins based on α-tocopherol (α-Toc) and fatty acids, and to compare their properties with those of α-tocopherol acetate (α-TAc).
  
  
  METHODS
  Skin levels of α-Toc-fatty acid ester conjugates, total α-Toc and endogenous α-Toc were measured in skin samples taken from separate groups of treated and untreated rats. Multiple and extensive treatment with α-Toc oleate and α-TAc was also carried out to assess the skin accumulation and safety of these esters.
  
  
  RESULTS
  The in-vivo studies revealed that α-Toc-fatty acid conjugates penetrated into the skin quantitatively while being comparable with the permeation of α-TAc. Differences were found between the levels of total α-Toc and endogenous α-Toc after application of α-TAc, α-Toc oleate, α-Toc linoleate, α-Toc-α linolenate and α-Toc palmitate, indicating that α-Toc conjugates of these fatty acids, but not α-Toc γ-linolenate or α-Toc stearate, were hydrolysed to free α-Toc. In long-term and extensive treatment, α-TAc was found to be lethal to rats treated with 1.15 mg/kg of this agent, which had been spread over 16 cm(2) of skin. Similar treatment with α-Toc oleate did not produce any side effects.
  
  
  CONCLUSIONS
  This study suggests that α-Toc conjugates with unsaturated fatty acids may be a good alternative as stable vitamin E derivatives, rather than the α-TAc ester.
authors.affiliation: Department of Pharmacology and School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Shimon
authors.initials: S
authors.lastname: Ben-Shabat
authors.forename: Yolia
authors.initials: Y
authors.lastname: Kazdan
authors.forename: Elie
authors.initials: E
authors.lastname: Beit-Yannai
authors.forename: Amnon C
authors.initials: AC
authors.lastname: Sintov
mesh_terms: D000085:Acetates / Q000378:metabolism* / Q000627:therapeutic use; D000287:Administration, Topical; D000818:Animals; D004952:Esters / Q000378:metabolism* / Q000627:therapeutic use; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D014810:Vitamin E / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use; D024502:alpha-Tocopherol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D000085:Acetates; D004952:Esters; D005231:Fatty Acids, Unsaturated; D014810:Vitamin E; D024502:alpha-Tocopherol