Generation of Tetrafluoroethylene-Propylene Elastomer-Based Microfluidic Devices for Drug Toxicity and Metabolism Studies

基于四氟乙烯-丙烯弹性体的微流体装置的生成,用于药物毒性和代谢研究

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作者:Emi Sano, Sayaka Deguchi, Naoki Matsuoka, Masahiro Tsuda, Mengyang Wang, Kaori Kosugi, Chihiro Mori, Keisuke Yagi, Aya Wada, Shinsuke Yamasaki, Tsuyoshi Kawai, Masahide Yodogawa, Hiroyuki Mizuguchi, Norihito Nakazawa, Fumiyoshi Yamashita, Yu-Suke Torisawa, Kazuo Takayama

Abstract

Polydimethylsiloxane (PDMS) is widely used to fabricate microfluidic organs-on-chips. Using these devices (PDMS-based devices), the mechanical microenvironment of living tissues, such as pulmonary respiration and intestinal peristalsis, can be reproduced in vitro. However, the use of PDMS-based devices in drug discovery research is limited because of their extensive absorption of drugs. In this study, we investigated the feasibility of the tetrafluoroethylene-propylene (FEPM) elastomer to fabricate a hepatocyte-on-a-chip (FEPM-based hepatocyte chip) with lower drug absorption. The FEPM-based hepatocyte chip expressed drug-metabolizing enzymes, drug-conjugating enzymes, and drug transporters. Also, it could produce human albumin. Although the metabolites of midazolam and bufuralol were hardly detected in the PDMS-based hepatocyte chip, they were detected abundantly in the FEPM-based hepatocyte chip. Finally, coumarin-induced hepatocyte cytotoxicity was less severe in the PDMS-based hepatocyte chip than in the FEPM-based hepatocyte chip, reflecting the different drug absorptions of the two chips. In conclusion, the FEPM-based hepatocyte chip could be a useful tool in drug discovery research, including drug metabolism and toxicity studies.

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