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学科主题: 药学
题名:
The P-glycoprotein inhibitory effect and related mechanisms of thiolated chitosan and its S-protected derivative
作者: Chen, Xianhui1; Zhang, Yang1; Yuan, Lan2; Zhang, Hua1; Dai, Wenbing1; He, Bing1; Wang, Xueqing1; Zhang, Qiang1,3
刊名: RSC ADVANCES
发表日期: 2015
DOI: 10.1039/c5ra19418k
卷: 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
所属项目编号: 81273456 ; 81473159 ; 2015CB932100
项目资助者: National Natural Science Foundation of China ; National Basic Research Program of China
WOS记录号: WOS:000366433700057
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63259
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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