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  [in Japanese] Development of a Liver-Gut device for the Evaluation of Drug Bioavailability  [in Japanese]

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Author(s)

Abstract

現在、医薬品のバイオアベイラビリティの<i>in vitro</i>での評価にはCaco-2細胞や凍結ヒト肝細胞などが用いられており、これら複数の評価系での試験結果を総合して予測がされている。しかしながら、このような方法では小腸と肝臓がまったく干渉しないと仮定されていることから、正確な予測には限界がある。近年、microphysiological systemが注目を浴びており、バイオアベイラビリティの予測や薬物相互作用研究、DDS研究など、創薬研究への応用も期待されている。本稿では、創薬研究への応用を目指して筆者らが行っているヒトiPS細胞由来小腸上皮細胞と小腸-肝臓2臓器連結デバイスの開発研究について紹介する。

The Caco-2 cell line, which is derived from human colon carcinoma, and the cryopreserved human primary hepatocytes are currently used as an <i>in vitro</i> 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

    THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

Codes

  • NII Article ID (NAID)
    130007772606
  • NII NACSIS-CAT ID (NCID)
    AN10084591
  • Text Lang
    JPN
  • ISSN
    0913-5006
  • NDL Article ID
    030000679
  • NDL Call No.
    Z19-1945
  • Data Source
    NDL  J-STAGE 
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