A Novel In Vitro Membrane Permeability Methodology Using Three-dimensional Caco-2 Tubules in a Microphysiological System Which Better Mimics In Vivo Physiological Conditions.

Autor:	Hagiwara Y; Analytical Research Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan., Kumagai H; Analytical Research Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan., Ouwerkerk N; European Analytical Research Laboratories, Astellas Pharma Europe B.V., Leiden 2333 BE, the Netherlands., Gijzen L; Mimetas B.V., Oegstgeest 2342 DH, the Netherlands., Annida R; Mimetas B.V., Oegstgeest 2342 DH, the Netherlands., Bokkers M; Mimetas B.V., Oegstgeest 2342 DH, the Netherlands., van Vught R; Mimetas B.V., Oegstgeest 2342 DH, the Netherlands., Yoshinari K; Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan., Katakawa Y; Analytical Research Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan., Motonaga K; Analytical Research Laboratories, Astellas Pharma Inc., Yaizu, Shizuoka 425-0072, Japan., Tajiri T; Pharmaceutical Science and Technology Laboratories, Astellas Pharma Inc., Tsukuba, Ibaraki 300-2698, Japan. Electronic address: tomokazu.tajiri@astellas.com.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2022 Jan; Vol. 111 (1), pp. 214-224. Date of Electronic Publication: 2021 Nov 25.
DOI:	10.1016/j.xphs.2021.11.016
Abstrakt:	The aim of this study was to develop an in vitro drug permeability methodology which mimics the gastrointestinal environment more accurately than conventional 2D methodologies through a three-dimensional (3D) Caco-2 tubules using a microphysiological system. Such a system offers significant advantages, including accelerated cellular polarization and more accurate mimicry of the in vivo environment. This methodology was confirmed by measuring the permeability of propranolol as a model compound, and subsequently applied to those of solifenacin and bile acids for a comprehensive understanding of permeability for the drug product in the human gastrointestinal tract. To protect the Caco-2 tubules from bile acid toxicity, a mucus layer was applied on the surface of Caco-2 tubules and it enables to use simulated intestinal fluid. The assessment using propranolol reproduced results equivalent to those obtained from conventional methodology, while that using solifenacin indicated fluctuations in the permeability of solifenacin due to various factors, including interaction with bile acids. We therefore suggest that this model will serve as an alternative testing system for measuring drug absorption in an environment closely resembling that of the human gastrointestinal tract. Competing Interests: Declaration of Interests None. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Yuki Hagiwara, Harumi Kumagai, Yoshifumi Katakawa, Kei Motonaga and Tomokazu Tajiri are employees of Astellas Pharma Inc. (Copyright © 2021. Published by Elsevier Inc.)
Databáze:	MEDLINE
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