基于微流控芯片的体外肠道吸收模型构建及其应用进展

Development and application of in vitro intestinal absorption model based on microfluidic chips

肠道是口服药物吸收的主要部位,肠道的上皮细胞上含有绒毛和微绒毛,它们通过增加表面积等因素促进分泌、细胞黏附和吸收。传统的二维/三维(2D/3D)细胞培养模型、动物模型在研究药物吸收方面发挥了重要作用,但是由于缺乏足够的人体药动学的可预测性或伦理问题等,其应用存在一定局限性。因此,以体外活细胞为基础,模拟人肠道的核心结构和关键功能是构建基于微流控芯片的肠道模型的研究重点。该模型是利用微加工技术制备出的模拟人体肠道的复杂微结构、微环境和生理功能的微流控芯片仿生系统。与2D细胞培养和动物实验相比,肠芯片模型能有效地模拟人体内环境,在药物筛选方面更具特异性。本综述概括了国内外肠芯片模型以及与肠道相关的多器官耦合芯片模型的研究进展,及其在疾病建模、药物吸收和转运方面的应用,并总结了当前肠芯片模拟肠道稳态和疾病面临的挑战,为进一步建立更可靠的体外肠芯片模型提供参考。

The intestine is the main site of oral drug absorption,and the epithelial cells of the intestine contain villi and microvilli,which promote secretion,cell adhesion,and absorption by increasing surface area and other factors.Traditional two-dimensional/three-dimensional(2D/3D)cell culture models and animal models have played an important role in studying drug absorption,but their application is limited due to the lack of sufficient predictability of human pharmacokinetics or ethical issues,etc.Therefore,mimicking the core structure and key functions of the human intestine based on in vitro live cells has been the focus of research on constructing a microfluidic chip-based intestinal model.The model is a microfluidic chip bionic system that simulates the complex microstructure,microenvironment,and physiological functions of the human intestine using microfabrication technology.Compared with 2D cell culture and animal experiments,the intestinal microarray model can effectively simulate the human in vivo environment and is more specific in drug screening.The research progress and applications in disease modeling,drug absorption and transport of intestinal microarray models and intestine-related multi-organ coupled microarray models at home and abroad were reviewed in this paper.The current challenges of intestinal chip simulating intestinal homeostasis and diseases were summarized,in order to provide reference for the further establishment of a more reliable in vitro intestinal chip model.