IR@PKUHSC  > 北京大学药学院
学科主题药学
The P-glycoprotein inhibitory effect and related mechanisms of thiolated chitosan and its S-protected derivative
Chen, Xianhui1; Zhang, Yang1; Yuan, Lan2; Zhang, Hua1; Dai, Wenbing1; He, Bing1; Wang, Xueqing1; Zhang, Qiang1,3
刊名RSC ADVANCES
2015
DOI10.1039/c5ra19418k
5期:126页:104228-104238
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary
研究领域[WOS]Chemistry
关键词[WOS]CACO-2 CELL MONOLAYERS ; EFFLUX PUMP INHIBITION ; IN-VIVO EVALUATION ; DRUG-DELIVERY ; ORAL DELIVERY ; MEDIATED EFFLUX ; ATPASE ACTIVITY ; MOLECULAR-MASS ; GP ; TRANSPORTERS
英文摘要

Thiolated polymers have attracted more and more attention for their prominent efflux pump inhibitory properties. The aim of this study was to unravel the P-glycoprotein (P-gp) inhibitory mechanisms mediated by new synthetic thiolated chitosan, chitosan-thioglycolic acid (CS-TGA) and its S-protected derivative (CS-TGA-6MNA). P-gp inhibitory activity was first assessed by determining rhodamine-123 (Rho-123) accumulation in Caco-2 cells, transportation across Caco-2 cell monolayers and across freshly excised rat intestine after exposure to CS-TGA or CS-TGA-6MNA. The results showed that after incubation with CS-TGA or CS-TGA-6MNA, a significant increase in intracellular Rho-123 level was observed in Caco-2 cells, more transportation in the absorptive (AP -> BL) direction and less transportation in the secretory (BL -> AP) direction of Rho-123 was observed in Caco-2 cell monolayers compared with DMEM solution control. In freshly excised rat intestine transportation, more Rho-123 was transported in a concentration-dependent manner. Then the P-gp inhibitory mechanisms were evaluated from four aspects: P-gp expression level, P-gp ATPase activity, intracellular ATP level and plasma membrane fluidity. No obvious changes in P-gp expression or intracellular ATP level were detected after exposure. However, the plasma membrane fluidization decreased and the P-gp ATPase activity reduced, which might contribute to the P-gp inhibitory effect. These features suggested this novel biomaterial might contribute to enhance the oral bioavailability of P-gp substrate drugs, such as cyclosporine A and paclitaxel.

语种英语
WOS记录号WOS:000366433700057
项目编号81273456 ; 81473159 ; 2015CB932100
资助机构National Natural Science Foundation of China ; National Basic Research Program of China
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63259
专题北京大学药学院
北京大学医学信息学中心
北京大学基础医学院
北京大学药学院_药剂学系
作者单位1.Peking Univ, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
2.Peking Univ, Med & Hlth Analyt Ctr, Beijing 100191, Peoples R China
3.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Chen, Xianhui,Zhang, Yang,Yuan, Lan,et al. The P-glycoprotein inhibitory effect and related mechanisms of thiolated chitosan and its S-protected derivative[J]. RSC ADVANCES,2015,5(126):104228-104238.
APA Chen, Xianhui.,Zhang, Yang.,Yuan, Lan.,Zhang, Hua.,Dai, Wenbing.,...&Zhang, Qiang.(2015).The P-glycoprotein inhibitory effect and related mechanisms of thiolated chitosan and its S-protected derivative.RSC ADVANCES,5(126),104228-104238.
MLA Chen, Xianhui,et al."The P-glycoprotein inhibitory effect and related mechanisms of thiolated chitosan and its S-protected derivative".RSC ADVANCES 5.126(2015):104228-104238.
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Chen, Xianhui]的文章
[Zhang, Yang]的文章
[Yuan, Lan]的文章
百度学术
百度学术中相似的文章
[Chen, Xianhui]的文章
[Zhang, Yang]的文章
[Yuan, Lan]的文章
必应学术
必应学术中相似的文章
[Chen, Xianhui]的文章
[Zhang, Yang]的文章
[Yuan, Lan]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。