Monocomponent hexa- and dodecaethylene glycol succinyl-tocopherol esters: Self-assembly structures, cellular uptake and sensitivity to enzyme hydrolysis

Britta M. Folmer, Denis Barron, Eric Hughes, Laurence Miguet, Belén Sanchez, Olivier Heudi, Martine Rouvet, Laurent Sagalowicz, Philippe Callier, Martin Michel, Gary Williamson

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

We have chemically synthesized two water-soluble forms of tocopherol succinate linked via an ester bond to hexaethylene glycol and dodecaethylene glycol. The self-assembly structure of the former in water is vesicular, whereas the latter forms elongated micelles. We treated Caco-2 cells with these compounds in these physical forms, in addition to a mixed micelle form. The intact compounds were taken up into the cells, influenced by both the chain length and the physical structure. In addition, the tocopherol derivatives were also metabolized into tocopherol succinate and tocopherol inside the cell. The total hydrolysis and uptake into the cells was two-fold higher from tocopherol hexaethylene glycol succinate in the form of mixed micelles than in vesicular form as assessed by analyzing intracellular tocopherol and tocopherol succinate. The longer polyethylene glycol chain gave a higher intracellular tocopherol succinate/tocopherol ratio. The major intracellular esterase in Caco-2 cells is carboxyl esterase 1 (EC 3.1.1.1), and in silico modelling studies show that the position of docking and hence the site of hydrolysis is influenced by the chain length. The in silico prediction is consistent with the in vitro data, since a longer chain length is predicted to favour hydrolysis of the ester bond between the succinate and polyethylene glycol moieties.

Original languageEnglish
Pages (from-to)1464-1474
Number of pages11
JournalBiochemical Pharmacology
Volume78
Issue number12
DOIs
Publication statusPublished - 15 Dec 2009
Externally publishedYes

Keywords

  • Caco-2 cell
  • Docking model
  • Esterase
  • Self-assembly structure
  • Vitamin E

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