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

Authors
  • Sano, Emi
  • Deguchi, Sayaka
  • Matsuoka, Naoki
  • Tsuda, Masahiro
  • Wang, Mengyang
  • Kosugi, Kaori
  • Mori, Chihiro
  • Yagi, Keisuke
  • Wada, Aya
  • Yamasaki, Shinsuke
  • Kawai, Tsuyoshi
  • Yodogawa, Masahide
  • Mizuguchi, Hiroyuki
  • Nakazawa, Norihito
  • Yamashita, Fumiyoshi
  • Torisawa, Yu-suke
  • Takayama, Kazuo
Publication Date
Sep 29, 2021
Source
Kyoto University Research Information Repository
Keywords
Language
English
License
Green
External links

Abstract

フッ素系エラストマー素材を用いた肝臓チップの開発と薬物代謝・毒性試験への応用. 京都大学プレスリリース. 2021-09-16. / Drug testing on miniatured livers. 京都大学プレスリリース. 2021-09-17. / 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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