Development of an Evaluation System Using Intestinal Organoids for Drug Efflux Transport Analysis by an Imaging Approach.

Autor:	Koseki C; School of Pharmaceutical Sciences and Pharmacy, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan., Ishikawa T; School of Pharmaceutical Sciences and Pharmacy, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan., Sato Y; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan., Shimada M; School of Pharmaceutical Sciences and Pharmacy, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan., Yokoi Y; Faculty of Advanced Life Science, Hokkaido University, Kita-21-jo, Nishi-11-chome, Kita-ku, Sapporo 001-0021, Japan., Nakamura K; Faculty of Advanced Life Science, Hokkaido University, Kita-21-jo, Nishi-11-chome, Kita-ku, Sapporo 001-0021, Japan., Honma N; Faculty of Health Sciences, Hokkaido University, Kita-12-jo, Nishi-5-chome, Kita-ku, Sapporo 060-0812, Japan., Moriyama T; Faculty of Health Sciences, Hokkaido University, Kita-12-jo, Nishi-5-chome, Kita-ku, Sapporo 060-0812, Japan., Kashiwagi H; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan., Sugawara M; Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan; Department of Pharmacy, Hokkaido University Hospital, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060-8648, Japan; Global Station for Biosurfaces and Drug Discovery, Global Institution for Research and Education (GI-CoRE), Hokkaido University, Japan. Electronic address: msuga@pharm.hokudai.ac.jp.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2024 Sep; Vol. 113 (9), pp. 2675-2682. Date of Electronic Publication: 2024 Jun 12.
DOI:	10.1016/j.xphs.2024.06.007
Abstrakt:	There are several in vitro systems that enable evaluation of the absorption direction, but there are few quantitative systems that enable easy evaluation of the excretion direction. Enteroids, organoids derived from intestine, have been frozen and passaged for various research. But it is not clear how the freezing and passaging affect the expression and function of transporters. We investigated the effects of passage and cryopreservation of enteroids. We focused on P-gp (P-glycoprotein) and compared the transfer rates of rhodamine 123 (Rh123) into the lumen of enteroids with and without a P-gp inhibitor. mRNA expression levels did not change significantly before and after passage and cryopreservation. Accumulation of Rh123 in the lumen of enteroids was observed. With some P-gp inhibitors, excretion of Rh123 into the lumen of enteroids was inhibited and the nonexcreted Rh123 accumulated in enteroids epithelial cells. The transfer rate of Rh123 into the lumen of enteroids with a P-gp inhibitor was significantly decreased compared to that of without a P-gp inhibitor. Before and after passage and cryopreservation, the transfer rate was almost the same as that of primary cultured enteroids. We succeeded in easily evaluating whether a component is a substrate of P-gp using enteroids. Competing Interests: Conflicts of interest The authors report no conflicts of interest in this work. (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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