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A fast screening model for drug permeability assessment based on native small intestinal extracellular matrix

文献类型：期刊论文

作者Li, Na2,3; Sui, Zhigang1; Liu, Yong4; Wang, Dandan2; Ge, Guangbo2; Yang, Ling2
刊名RSC ADVANCES
出版日期2018
卷号8期号:60页码:34514-34524
ISSN号2046-2069
DOI10.1039/c8ra05992f
通讯作者Ge, Guangbo(geguangbo@shutcm.edu.cn) ; Yang, Ling(yling@dicp.ac.cn)
英文摘要The Caco-2 cell monolayer model is widely utilized to predict drug permeability across human intestinal epithelial cells. However, at least 21 days is required for the formation and maturation of a well-tight Caco-2 cell monolayer, thereby restricting the throughput of the screening model during drug discovery. To address this challenge, a fast (7 days), and more physiologically relevant screening model integrating both the Caco-2 cell model and a small intestinal submucosa (SIS) hydrogel was developed in this study. The 7 day model exhibited desirable phenotype and functional similarity to the conventional 21 day Caco-2 model with respect to paracellular resistance, alkaline phosphatase (ALP) activities, and the mRNA expression level of three transporters (PEPT1, OATP1A2, and P-gp) as well as their mediated influx or efflux. Besides, the increased gene expression of two excretive transporters (BCRP, MRP2) and their enhanced functionality were observed in the current fast model compared to the traditional 21 day model. More importantly, a strong correlation (r(2) = 0.9458) was obtained between the absorptive P app values of 19 model compounds in the 7 day model and those in the conventional 21 day model. These results revealed the pivotal role of the native extracellular matrix (SIS) in facilitating the differentiation of Caco-2 cells, leading to the reconstruction of the accelerated 7 day model, which presents a promising tool for screening drug permeability in future drug discovery.
WOS关键词CELL-ECM INTERACTIONS ; IN-VITRO ; CACO-2 CELL ; EPITHELIAL-CELLS ; GROWTH-FACTOR ; STEM-CELLS ; DIFFERENTIATION ; EXPRESSION ; SUBMUCOSA ; TRANSPORT
资助项目National Key Research and Development Program of China[2017YFC1700200] ; National Key Research and Development Program of China[2017YFC1702000] ; NSF of China[81473181] ; NSF of China[81773687] ; NSF of China[81703604] ; NSF of China[81672961] ; NSF of China[81573501] ; Program of Shanghai Academic/Technology Research Leader[18XD1403600] ; National Scientific and Technological Major Projects of China[2017ZX09101004] ; Innovative Entrepreneurship Program of High-level Talents in Dalian[2016RQ025] ; Innovative Entrepreneurship Program of High-level Talents in Dalian[2017RQ121]
WOS研究方向Chemistry
语种英语
WOS记录号WOS:000448423500039
出版者ROYAL SOC CHEMISTRY
资助机构National Key Research and Development Program of China ; National Key Research and Development Program of China ; NSF of China ; NSF of China ; Program of Shanghai Academic/Technology Research Leader ; Program of Shanghai Academic/Technology Research Leader ; National Scientific and Technological Major Projects of China ; National Scientific and Technological Major Projects of China ; Innovative Entrepreneurship Program of High-level Talents in Dalian ; Innovative Entrepreneurship Program of High-level Talents in Dalian ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; NSF of China ; NSF of China ; Program of Shanghai Academic/Technology Research Leader ; Program of Shanghai Academic/Technology Research Leader ; National Scientific and Technological Major Projects of China ; National Scientific and Technological Major Projects of China ; Innovative Entrepreneurship Program of High-level Talents in Dalian ; Innovative Entrepreneurship Program of High-level Talents in Dalian ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; NSF of China ; NSF of China ; Program of Shanghai Academic/Technology Research Leader ; Program of Shanghai Academic/Technology Research Leader ; National Scientific and Technological Major Projects of China ; National Scientific and Technological Major Projects of China ; Innovative Entrepreneurship Program of High-level Talents in Dalian ; Innovative Entrepreneurship Program of High-level Talents in Dalian ; National Key Research and Development Program of China ; National Key Research and Development Program of China ; NSF of China ; NSF of China ; Program of Shanghai Academic/Technology Research Leader ; Program of Shanghai Academic/Technology Research Leader ; National Scientific and Technological Major Projects of China ; National Scientific and Technological Major Projects of China ; Innovative Entrepreneurship Program of High-level Talents in Dalian ; Innovative Entrepreneurship Program of High-level Talents in Dalian
源URL[http://cas-ir.dicp.ac.cn/handle/321008/166746]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Ge, Guangbo; Yang, Ling
作者单位1.Chinese Acad Sci, Dalian Inst Chem Phys, Dalian 116023, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai 201203, Peoples R China
3.Univ South Dakota, Dept Biomed Engn, Sioux Falls, SD 57107 USA
4.Dalian Univ Technol, Sch Life Sci & Med, Panjin 124221, Peoples R China
推荐引用方式
GB/T 7714		 Li, Na,Sui, Zhigang,Liu, Yong,et al. A fast screening model for drug permeability assessment based on native small intestinal extracellular matrix[J]. RSC ADVANCES,2018,8(60):34514-34524.
APA Li, Na,Sui, Zhigang,Liu, Yong,Wang, Dandan,Ge, Guangbo,&Yang, Ling.(2018).A fast screening model for drug permeability assessment based on native small intestinal extracellular matrix.RSC ADVANCES,8(60),34514-34524.
MLA Li, Na,et al."A fast screening model for drug permeability assessment based on native small intestinal extracellular matrix".RSC ADVANCES 8.60(2018):34514-34524.

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来源：大连化学物理研究所

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