北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学药学院  > 药剂学系  > 期刊论文
学科主题: 药学
题名:
Inhibition Mechanism of P-glycoprotein Mediated Efflux by mPEG-PLA and Influence of PLA Chain Length on P-glycoprotein Inhibition Activity
作者: Li, Wenjing1; Li, Xinru1; Gao, Yajie1; Zhou, Yanxia1; Ma, Shujin1; Zhao, Yong1; Li, Jinwen1; Liu, Yan1; Wang, Xinglin2; Yin, Dongdong2
关键词: mPEG-PLA ; block copolymer ; P-glycoprotein efflux ; inhibition mechanism ; Caco-2 cells
刊名: MOLECULAR PHARMACEUTICS
发表日期: 2014
DOI: 10.1021/mp4004223
卷: 11, 期:1, 页:71-80
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]: Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]: CACO-2 CELL MONOLAYERS ; PLURONIC BLOCK-COPOLYMERS ; VITAMIN-E TPGS ; BREAST-CANCER CELLS ; ATPASE ACTIVITY ; IN-VITRO ; MEMBRANE FLUIDIZATION ; FLUORESCENCE POLARIZATION ; TRANSPORT MECHANISM ; DIBLOCK COPOLYMERS
英文摘要:

The present study aimed to investigate the effect of monomethoxy poly(ethylene glycol)-block-poly(D,L-lactic acid) (mPEG-PLA) on the activity of P-glycoprotein (P-gp) in Caco-2 cells and further unravel the relationship between PLA chain length in mPEG-PLA and influence on P-gp efflux and the action mechanism. The transport results of rhodamine 123 (R123) across Caco-2 cell monolayers suggested that mPEG-PLA unimers were responsible for its P-gp inhibitory effect. Furthermore, transport studies of R123 revealed that the inhibitory potential of P-gp efflux by mPEG-PLA analogues was strongly correlated with their structural features and showed that the hydrophilic mPEG-PLA copolymers with an intermediate PLA chain length and 10.20 of hydrophilic-lipophilic balance were more effective at inhibiting P-gp efflux in Caco-2 cells. The fluorescence polarization measurement results ruled out the plasma membrane fluidization as a contributor for inhibition of P-gp by mPEG-PLA. Concurrently, mPEG-PLA inhibited neither basal P-gp ATPase (ATP is adenosine triphosphate) activity nor substrate stimulated P-gp ATPase activity, suggesting that mPEG-PLA seemed not to be a substrate of P-gp and a competitive inhibitor. No evident alteration in P-gp surface level was detected by flow cytometry upon exposure of the cells to mPEG-PLA. The depletion of intracellular ATP, which was likely to be a result of partial inhibition of cellular metabolism, was directly correlated with inhibitory potential for P-gp mediated efflux by mPEG-PLA analogues. Hence, intracellular ATP-depletion appeared to be possible explanation to the inhibition mechanism of P-gp by mPEG-PLA. Taken together, the establishment of a relationship between PLA chain length and impact on P-gp efflux activity and interpretation of action mechanism of mPEG-PLA on P-gp are of fundamental importance and will facilitate future development of mPEG-PLA in the drug delivery area.

语种: 英语
所属项目编号: 81172990 ; 2009CB930300 ; BMU20110263
项目资助者: National Natural Science Foundation of China ; National Key Science Research Program of China (973 program) ; Innovation Team of Ministry of Education ; State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research
WOS记录号: WOS:000329529700007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56812
Appears in Collections:北京大学药学院_药剂学系_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China
2.Tianjin Inst Pharmaceut Res, State Key Lab Drug Delivery Technol & Pharmacokin, Tianjin 300193, Peoples R China

Recommended Citation:
Li, Wenjing,Li, Xinru,Gao, Yajie,et al. Inhibition Mechanism of P-glycoprotein Mediated Efflux by mPEG-PLA and Influence of PLA Chain Length on P-glycoprotein Inhibition Activity[J]. MOLECULAR PHARMACEUTICS,2014,11(1):71-80.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Li, Wenjing]'s Articles
[Li, Xinru]'s Articles
[Gao, Yajie]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Li, Wenjing]‘s Articles
[Li, Xinru]‘s Articles
[Gao, Yajie]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace