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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
- 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.
- Subjects :
- Cell Membrane Permeability
Bile acid
Membrane permeability
Chemistry
medicine.drug_class
Human gastrointestinal tract
Pharmaceutical Science
Permeability
In vitro
Intestinal fluid
Bile Acids and Salts
Gastrointestinal Tract
medicine.anatomical_structure
Intestinal Absorption
Caco-2
Permeability (electromagnetism)
In vivo
medicine
Biophysics
Humans
Caco-2 Cells
Subjects
Details
- ISSN :
- 00223549
- Volume :
- 111
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....536eaebc2e2e2421c39c2c797264f2bf