首页 > 新闻中心 > 文章速递
Enhancing the intestinal absorption of low molecular weight chondroitin sulfate by conjugation with a-linolenic acid and the transport mechanism of the conjugates
发表时间:2015-02-05 09:07:19

Yuliang Xiao , Pingli Li , Yanna Cheng , Xinke Zhang , Juzheng Sheng , Decai Wang , Juan Li , Qian Zhang , Chuanqing Zhong , Rui Cao , Fengshan Wang

International Journal of Pharmaceutics 465 (2014) 143–158

ABSTRACT

The purpose of this report was to demonstrate the effect of amphiphilic polysaccharides-based selfassembling micelles on enhancing the oral absorption of low molecular weight chondroitin sulfate (LMCS) in vitro and in vivo, and identify the transepithelial transport mechanism of LMCS micelles across the intestinal barrier. a-Linolenic acid-low molecular weight chondroitin sulfate polymers(a-LNA–LMCS) were successfully synthesized, and characterized by FTIR, 1HNMR, TGA/DSC, TEM, laser light scattering and zeta potential. The significant oral absorption enhancement and elimination half-life (t1/2) extension of LNA–LMCS2 in rats were evidenced by intragastric administration in comparison with CS and LMCS. Caco-2 transport studies demonstrated that the apparent permeability coefficient (Papp) of LNA–LMCS2 was significantly higher than that of CS and LMCS (p < 0.001), and no significant effects on the overall integrity of the monolayer were observed during the transport process. In addition, a-LNA–LMCS micelles accumulated around the cell membrane and intercellular space observed by confocal laser scanning microscope (CLSM). Furthermore, evident alterations in the F-actin cytoskeleton were detected by CLSM observation following the treatment of the cell monolayers with a-LNA–LMCS micelles, which further certified the capacity of a-LNA–LMCS micelles to open the intercellular tight junctions rather than disrupt the overall integrity of the monolayer. Therefore, LNA–LMCS2 with low cytotoxicity and high bioavailability might be a promising substitute for CS in clinical use, such as treating osteoarthritis, atherosclerosis, etc.

Copyright 2012-2013 www.glycoeng.sdu.edu.cn All Rights Reserved. 山东大学国家糖工程技术研究中心 版权所有 技术支持:齐鲁八达

地址:山东省济南市山大南路27号  电话:0531-88363002  邮箱:glycoengineering@sdu.edu.cn