标题:N-mercapto acetyl-N′-octyl-O, N″-glycol chitosan as an efficiency oral delivery system of paclitaxel
作者:Huo M.; Fu Y.; Liu Y.; Chen Q.; Mu Y.; Zhou J.; Li L.; Xu W.;等
作者机构:[Huo, M] State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, Ch 更多
通讯作者:Xu, W(weixu@sdu.edu.cn)
通讯作者地址:[Xu, W] Department of Pharmacy, Shandong Provincial Qian Foshan Hospital, Shandong UniversityChina;
来源:Carbohydrate Polymers
出版年:2018
卷:181
页码:477-488
DOI:10.1016/j.carbpol.2017.10.066
关键词:Micelles; Mucoadhesion; N-mercapto acetyl-N′-octyl-O, N″-glycol chitosan; Oral delivery; P-glycoprotein; Paclitaxel
摘要:Herein, thioglycolic acid modified N-octyl-O, N′-glycol chitosan (N-mercapto acetyl-N′-octyl-O, N″-glycol chitosan, abbreviated as SH-OGC) was synthesized to improve the oral bioavailability of paclitaxel (PTX). PTX was readily solubilized into the hydrophobic inner core of SH-OGC. Pharmacokinetic studies demonstrated that the bioavailability of PTX was greatly enhanced when delivered by SH-OGC compared to Taxol® or non-sulfhydrylated OGC micelles. Caco-2 cell experiments confirmed PTX or rhodamine-123-loaded SH-OGC demonstrated effective cellular accumulation via caveola-mediated endocytosis along with the inhibition of P-gp efflux. Furthermore, Caco-2 transport studies demonstrated that the mechanistic basis of SH-OGC efficacy was attributed to P-gp inhibition, enhanced permeability of tight junctions and clathrin-mediated transcytosis across the endothelium. In addition, SH-OGC exhibited increased intestinal retention through thiol-mediated mucoadhesion compared with OGC according to results of mucoadhesion evaluation on freshly excised rat intestine. In summary, SH-OGC micelles may present as a promising delivery vehicle for enhancing the oral bioavailability of P-gp substrates. © 2017 Elsevier Ltd
收录类别:SCOPUS
Scopus被引频次:1
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032788865&doi=10.1016%2fj.carbpol.2017.10.066&partnerID=40&md5=24d75c5ddfce54a883d333404688f8fc
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