Development of a Liver-Gut device for the Evaluation of Drug Bioavailability

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  • 肝臓－小腸を接続したバイオアベイラビリティ評価システムの開発
  • カンゾウ-ショウチョウ オ セツゾク シタ バイオアベイラビリティ ヒョウカ システム ノ カイハツ

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Abstract

The Caco-2 cell line, which is derived from human colon carcinoma, and the cryopreserved human primary hepatocytes are currently used as an in vitro model for evaluating the bioavailability of orally administrated drugs. The bioavailability is predicted by integrating pharmacokinetic data obtained from these evaluation systems. However, the evaluation systems are limited to predicting bioavailability of drugs in humans, since it is hypothesized that both the small intestine and liver do not interfere with each other. The Caco-2 cell line is partially similar to the small intestine in morphology and in expression and function of efflux transporters. On the other hand, drug-metabolizing enzyme activities and robustness of tight junctions are dramatically different from those of the small intestine. Therefore, it is necessary to develop novel prediction systems for drug bioavailability, such as small intestinal epithelial cell-like cells as an alternative to Caco-2 cells. In addition, a microphysiological system has been a recent topic of interest, and is expected to have various applications in drug development studies, such as prediction of bioavailability, drug-drug interactions, and research on the drug delivery system. In this review, we describe our research regarding the development of small intestinal epithelial cells differentiated from human induced pluripotent stem cells and liver-gut device.

Journal

  • Drug Delivery System

    Drug Delivery System 34 (4), 249-260, 2019-09-25

    THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

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