Pharmaceutical Analysis, Department of Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Integr Biol (Camb). 2011 May;3(5):509-21. doi: 10.1039/c0ib00119h. Epub 2011 Feb 17.
Microfluidic technologies enable the fabrication of advanced in vitro systems incorporating liver tissue or cells to perform metabolism and toxicity studies for drugs and other xenobiotics. The use of microfluidics provides the possibility to utilize a flow of medium, thereby creating a well-controlled microenvironment. The general goals of most in vitro systems in drug research are to optimally mimic the in vivo situation, and to minimize the number of animals required for preclinical studies. Moreover, they may contribute to a reduced attrition rate of drugs at a late stage of the drug development process; this is especially true if human tissue or cells are used. A number of factors are important in achieving good in vivo predictability in microfluidic systems, of which the biological system itself (cells or tissue) and the incubation conditions are the most important. The last couple of years have seen various microfluidic-based in vitro systems being developed to incorporate many different cells and/or tissues. In this review, microfluidics-based in vitro systems realized to study liver metabolism and toxicity are summarized and discussed with respect to their applications, advantages, and limitations. The biological basis of these systems is evaluated, and incubation conditions considered. Precise control of the cell or tissue microenvironment is a key advantage of using microfluidic technologies, and the benefits of exposing the cells to medium flow are demonstrated. Special attention is also paid to the incorporation of multiple cell types or tissues into a microfluidic device for the investigation of interorgan interactions, which are difficult if not impossible to study in conventional systems.
微流控技术能够制造出包含肝脏组织或细胞的先进体外系统，用于进行药物和其他外源物质的代谢和毒性研究。微流控的使用提供了利用介质流动的可能性，从而创造出一个良好控制的微环境。大多数药物研究体外系统的总体目标是最佳模拟体内情况，并尽量减少临床前研究所需的动物数量。此外，如果使用人类组织或细胞，它们可能有助于降低药物在药物开发过程后期的淘汰率。在实现微流控系统中良好的体内预测性方面，有许多因素很重要，其中最重要的是生物系统本身（细胞或组织）和孵育条件。在过去的几年中，已经开发出了各种基于微流控的体外系统，以整合许多不同的细胞和/或组织。本文总结并讨论了用于研究肝脏代谢和毒性的基于微流控的体外系统，讨论了它们的应用、优点和局限性。评估了这些系统的生物学基础，并考虑了孵育条件。精确控制细胞或组织的微环境是使用微流控技术的一个关键优势，并且证明了使细胞暴露于介质流的好处。特别关注将多种细胞类型或组织纳入微流控设备中，以研究器官间相互作用，这在传统系统中是难以甚至不可能研究的。
