Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation

	Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation
	Li, Na 1,2; Wang, Dandan 1,2; Sui, Zhigang 3; Qi, Xiaoyi 4; Ji, Liyun 1; Wang, Xiuli 3; Yang, Ling 1
刊名	tissue engineering part c-methods
	2013-09-01
卷号	19 期号:9 页码:708-719
通讯作者	杨凌
产权排序	待补充
合作状况	英
英文摘要	human epithelial cell culture models of monolayer caco-2 cells have been widely employed to assess the absorption of drug molecules across intestinal mucosa. however, cautions should be taken when interpreting the conclusions from those models due to their undesirable phenotype and functionality when compared with the native intestinal tissue. in the present study, an improved, more physiologically relevant three-dimensional (3d) culture model of the intestinal mucosa was developed to study drug absorption, in which a coculture of epithelial cells, including caco-2 cells and ht29-methotrexate cells, was indirectly seeded on a transwell filter insert with collagen gel and stromal cells (fibroblasts and immunocytes) incorporation. this setting-up provided a compatible environment to improve the phenotype and functionality of the epithelial cells. compared with the monolayer culture of caco-2 cells, the reconstructed 3d model displayed more physiologically relevant characteristics evidenced by its decreased teer value and mucus-like layer formation. a decreased expression of p-gp and an increased expression of bcrp were also observed in the current 3d culture model, leading to a changed secretory permeability of their substrates. more importantly, an improved correlation (r-2 = 0.843) was obtained between the absorptive permeability across the 3d coculture model and the human absorption fraction especially for those model compounds with moderate or high permeability. thus, this engineered 3d coculture model presents a unique, improved opportunity to evaluate drug permeability in vitro.
学科主题	物理化学
WOS标题词	science & technology ; life sciences & biomedicine
类目[WOS]	cell & tissue engineering ; biotechnology & applied microbiology ; cell biology
研究领域[WOS]	cell biology ; biotechnology & applied microbiology
关键词[WOS]	caco-2 cell monolayers ; epithelial-cells ; growth-factor ; permeability ; transport ; prediction ; humans ; assay ; proliferation ; discovery
收录类别	SCI
资助信息	1，1
原文出处	719
语种	英语
WOS记录号	WOS:000322117900005
公开日期	2014-09-11
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/119621]
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
作者单位	1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Chinese Acad Sci, Dalian Inst Chem Phys, Dept Biotechnol, Dalian 116023, Peoples R China 4.Dalian Med Univ, Hosp 2, Dalian, Peoples R China
推荐引用方式 GB/T 7714	Li, Na,Wang, Dandan,Sui, Zhigang,et al. Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation[J]. tissue engineering part c-methods,2013,19(9):708-719.
APA	Li, Na.,Wang, Dandan.,Sui, Zhigang.,Qi, Xiaoyi.,Ji, Liyun.,...&Yang, Ling.(2013).Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation.tissue engineering part c-methods,19(9),708-719.
MLA	Li, Na,et al."Development of an Improved Three-Dimensional In Vitro Intestinal Mucosa Model for Drug Absorption Evaluation".tissue engineering part c-methods 19.9(2013):708-719.