Influence on intestinal mucous permeation of paclitaxel of absorption enhancers and dosage forms based on electron spin resonance spectroscopy.
The aim of this paper is to investigate the permeation mechanism of the hydrophobic drug, paclitaxel in intestinal membranes of mice in relation to enhancers and preparation factors. The alteration fluidity of lipid and protein in mucous membrane were determined using electron spin resonance (ESR) when the membrane was treated with several enhancers including Pluronic F68, polyethylene glycol (PEG), Brij78 and lecithin. At the same time, the enhanced permeation of paclitaxel across the intestinal intercellular membrane of stratum corneum was studied for three formulations: inclusion complex, microemulsion and injection. The results showed that use of paclitaxel-hydroxypropyl-beta-cyclodextrin inclusion complexation and of paclitaxel microemulsion as vehicle and PEG 1500 as enhancer could significantly increase the permeation kinetics of paclitaxel in a fluid diffusion study. The effect on absorption characteristics of enhancing permeation of this hydrophobic drug in the intestinal mucosa was considered in the light of the change in membrane fluid.
Zhang
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XN
College of Pharmacy, Soochow University, DuShuHu High Education Zone, Su Zhou, Jiang Su Province, People's Republic of China. zhangxuenong@163.com
Xu
J
J
Tang
L H
LH
Gong
J
J
Yan
X Y
XY
Zhang
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Q
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000465:Algorithms; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics*; D003497:Cyclic N-Oxides / Q000737:chemistry; D004058:Diffusion; D004304:Dosage Forms; D004578:Electron Spin Resonance Spectroscopy; D004655:Emulsions; D006207:Half-Life; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D017239:Paclitaxel / Q000737:chemistry / Q000493:pharmacokinetics*; D010539:Permeability; D014677:Pharmaceutical Vehicles; D013113:Spin Labels; D013347:Subcellular Fractions / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D003497:Cyclic N-Oxides; D004304:Dosage Forms; D004655:Emulsions; D014677:Pharmaceutical Vehicles; D013113:Spin Labels; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C005072:5-doxylstearic acid; C032363:16-nitroxystearic acid; D017239:Paclitaxel