I608, Department of Chemical Engineering, Hongik University, Sangsu-dong, Mapo-gu, Seoul, Republic of Korea.
Enzyme Microb Technol. 2013 Aug 15;53(3):159-64. doi: 10.1016/j.enzmictec.2013.02.015. Epub 2013 Mar 7.
Biotransformation in the liver plays an important role in determining the pharmacokinetic profile of drugs and food components. Current in vitro platforms for testing the liver metabolism suffers from the lack of resemblance to the human liver metabolism, mainly due to the lost metabolic activity of cultured hepatocytes and the absence of transport phenomena that occurs in the liver tissue. Here we report a microfluidic device with liver microsome encapsulated in 3-D hydrogel matrix, which can mimic the metabolism reaction and the transport phenomena in the liver. Photopolymerization of poly(ethylene glycol) diacrylate (PEG-DA) allows controlling the mass transfer with matrix sizes, and a gravity-induced passive flow can reproduce the blood flow through the liver. We measured the reaction kinetics of P450 enzymes in the device, and simulated the convection-diffusion-reaction characteristics inside the device with a mathematical model. Combination of mathematical analytical tool and the experimental tool allowed us to analyze and optimize the reaction kinetics inside the microfluidic chip. This novel in vitro platform can serve as a tool for screening the liver metabolism of various compounds.
肝脏中的生物转化在决定药物和食物成分的药代动力学特征方面起着重要作用。目前用于测试肝脏代谢的体外平台由于缺乏与人肝脏代谢的相似性而受到限制，主要是由于培养的肝细胞失去了代谢活性，以及在肝组织中不存在运输现象。在这里，我们报告了一种将肝微粒体包封在 3D 水凝胶基质中的微流控装置，该装置可以模拟肝脏中的代谢反应和运输现象。聚乙二醇二丙烯酸酯（PEG-DA）的光聚合允许通过基质尺寸控制质量传递，并且重力诱导的被动流可以再现肝血流。我们在该装置中测量了 P450 酶的反应动力学，并使用数学模型模拟了装置内的对流-扩散-反应特性。数学分析工具和实验工具的组合使我们能够分析和优化微流控芯片内的反应动力学。这种新型的体外平台可以作为筛选各种化合物在肝脏中代谢的工具。
