The past, present and future of intestinal in vitro cell systems for drug absorption studies

  • The intestinal epithelium acts as a selective barrier for the absorption of water, nutrients and orally administered drugs. To evaluate the gastrointestinal permeability of a candidate molecule, scientists and drug developers have a multitude of cell culture models at their disposal. Static transwell cultures constitute the most extensively characterized intestinal in vitro system and can accurately categorize molecules into low, intermediate and high permeability compounds. However, they lack key aspects of intestinal physiology, including the cellular complexity of the intestinal epithelium, flow, mechanical strain, or interactions with intestinal mucus and microbes. To emulate these features, a variety of different culture paradigms, including microfluidic chips, organoids and intestinal slice cultures have been developed. Here, we provide an updated overview of intestinal in vitro cell culture systems and critically review their suitability for drug absorption studies. The available data show that these advanced culture models offer impressive possibilities for emulating intestinal complexity. However, there is a paucity of systematic absorption studies and benchmarking data and it remains unclear whether the increase in model complexity and costs translates into improved drug permeability predictions. In the absence of such data, conventional static transwell cultures remain the current gold-standard paradigm for drug absorption studies.

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Author:Sonia Youhanna, Volker Martin Lauschke
URN:urn:nbn:de:hebis:30:3-623863
DOI:https://doi.org/10.1016/j.xphs.2020.07.001
ISSN:1520-6017
Parent Title (English):Journal of Pharmaceutical Sciences
Publisher:Elsevier
Place of publication:Amsterdam
Document Type:Article
Language:English
Date of Publication (online):2020/07/03
Date of first Publication:2020/07/03
Publishing Institution:Universit├Ątsbibliothek Johann Christian Senckenberg
Release Date:2021/08/03
Tag:Bioavailability prediction; Drug permeability; Microfluidics; Microphysiological models; Organoids; Preclinical drug development
Volume:110.2021
Issue:1
Page Number:16
First Page:50
Last Page:65
HeBIS-PPN:489232493
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universit├Ątspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0