Abstract
Microphysiological system (MPS) begins to penetrate the field of drug development as an evaluation system that is expected to have various strengths, such as the high extrapolation properties and the alternative methods to animal. Compared to conventional in vitro assays, perfusion by microfluidic channels and three-dimensional tissue arrangement are possible, which increases the difficulty of operation and poses many challenges until implementation as a robust assay system. In the AMED, we aim to solve such issues in the operation of MPS and are obtaining qualification data for MPS (enterohepatic linkage, gastrointestinal and blood-brain barrier).
As for the enterohepatic linkage MPS, the evaluation of "MS-plate" developed by Prof. Matsunaga at Nagoya City University is underway. It is a culture system that carries enterocytes and hepatocytes and is connected by perfusion, enabling examination of the first pass effect. For gastrointestinal MPS, Prof. Kimura at Tokai University have developed a microfluidic chip "Fluid3D-X®" with enterocytes seeded porous membrane and obtaining various pharmacokinetic data to evaluate the system. In addition, we are currently qualifying the function of the "BBB-NET" developed by Prof. Matsuzaki at Osaka University as a blood-brain barrier MPS, which is expected to be used as a receptor-mediated transport model. Currently, we are understanding the users' context of use, optimizing assay processes such as cells, seeding, culture medium, and culture conditions, and qualifying the absorption and metabolism as indices. In particular, by obtaining data on Repeatability Test and Intermediate Precision Test, we are also clarifying the variation factors in the assay process. In this presentation, we will introduce the results of the qualification and our efforts to create a robust assay system.
