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N-mercapto acetyl-N′-octyl-O, N″-glycol chitosan as an efficiency oral delivery system of paclitaxel.
- Source :
-
Carbohydrate Polymers . Feb2018, Vol. 181, p477-488. 12p. - Publication Year :
- 2018
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01448617
- Volume :
- 181
- Database :
- Academic Search Index
- Journal :
- Carbohydrate Polymers
- Publication Type :
- Academic Journal
- Accession number :
- 126738128
- Full Text :
- https://doi.org/10.1016/j.carbpol.2017.10.066