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

Authors :
Linda Gijzen
Kouichi Yoshinari
Niels Ouwerkerk
Kei Motonaga
Marleen Bokkers
Yuki Hagiwara
Remko van Vught
Harumi Kumagai
Tomokazu Tajiri
Rumaisha Annida
Yoshifumi Katakawa
Source :
Journal of Pharmaceutical Sciences. 111:214-224
Publication Year :
2022
Publisher :
Elsevier BV, 2022.

Abstract

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.

Details

ISSN :
00223549
Volume :
111
Database :
OpenAIRE
Journal :
Journal of Pharmaceutical Sciences
Accession number :
edsair.doi.dedup.....536eaebc2e2e2421c39c2c797264f2bf