Influence of vitamin E TPGS poly(ethylene glycol) chain length on apical. efflux transporters in Caco-2 cell monolayers

被引：158

作者：

Collnot, EM

Baldes, C

Wempe, MF

Hyatt, J

Navarro, L

Edgar, KJ

Schaefer, UF

Lehr, CM ^{[1
]}

机构：

[1] Univ Saarland, Dept Biopharmaceut & Pharmaceut Technol, D-66123 Saarbrucken, Germany

[2] Eastman Chem Co, Kingsport, TN 37662 USA

来源：

JOURNAL OF CONTROLLED RELEASE | 2006年 / 111卷 / 1-2期

关键词：

P-glycoprotein; vitamin E TPGS; absorption enhancer; poly(ethylene glycol); Caco-2;

D O I：

10.1016/j.jconrel.2005.11.005

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(D)-alpha-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS 1000) is a widely used form of vitamin E. TPGS 1000 is comprised of a hydrophilic polar (water-soluble) head and a lipophilic (water-insoluble) alkyl tail. TPGS 1000 has been used as a solubilizer, an emulsifier and as a vehicle for lipid-based drug delivery formulations. Most recently, TPGS 1000 has been recognized as an effective oral absorption enhancer. An enhancing effect is consistent with a surfactant-induced inhibition of P-glycoprotein (P-gp), and perhaps other drug transporter proteins; however, the exact inhibition mechanism(s) remain unclear. Therefore, in an attempt to generate additional knowledge, we have synthesized and tested various TPGS analogs containing different PEG chain length (TPGS 200/238/400/600/1000/2000/3400/3500/4000/6000). These results demonstrate a relationship between TPGS PEG chain length and influence on rhodamine 123 (RHO) transport in Caco-2 monolayers, a relationship which may be illustrated using a Weibull distribution. (c) 2005 Elsevier B.V. All rights reserved.

引用

页码：35 / 40

页数：6

共 41 条

[21] Relationships between the hydrophilic-lipophilic balance values of pharmaceutical excipients and their multidrug resistance modulating effect in Caco-2 cells and rat intestines [J].