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Updated: Dec 27, 2025
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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
8.4K
Developing in vitro assays to transform gastrointestinal safety assessment: potential for microphysiological systems
Matthew F Peters1, Allison L Choy, Carmen Pin
1Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Boston, USA. matt.peters@astrazeneca.com.
Lab on a Chip
|March 5, 2020
Summary
Developing advanced 3D gastrointestinal (GI) microtissues, including organoids and organ-on-a-chip systems, offers a promising solution for early detection of drug-induced gastrointestinal toxicities (DI-GITs). These novel in vitro models better recapitulate gut physiology for improved drug safety assessment.
Area of Science:
- * Pharmacology
- * Toxicology
- * Biomedical Engineering
Background:
- * Drug-induced gastrointestinal toxicities (DI-GITs) are common adverse events in clinical trials, hindering drug development.
- * Current experimental tools lack the robustness for early DI-GIT detection and safer molecule optimization.
- * Recapitulating complex gut physiology requires integrating diverse cell types (epithelial, immune, microbiome, nerve, muscle), which is challenging for traditional 2D cell cultures.
Purpose of the Study:
- * To review current approaches for assessing pharmaceutical GI toxicity.
- * To compare existing methods with the capabilities of emerging GI microtissues (organoids, organ-on-a-chip, transwell systems).
- * To identify necessary assay features for microphysiological systems (MPS) adoption in DI-GIT assessment.
Main Methods:
- * Review of existing literature on GI toxicity assessment methods.
- * Analysis of emerging 3D GI microtissue models, including organoids and microfluidic systems.
- * Comparison of microtissue capabilities with the requirements for DI-GIT assessment.
Main Results:
- * Emerging 3D GI microtissues, particularly organoids and microfluidic-based systems, can self-organize and differentiate into various intestinal cell types.
- * Co-culture models incorporating organoids or microtissues with non-epithelial cells can reproduce complex cross-tissue interactions.
- * These advanced models show potential for accurately studying drug-induced toxicities by mimicking in vivo gut microphysiology.
Conclusions:
- * 3D GI microtissues represent a significant advancement over traditional 2D models for studying DI-GITs.
- * Microphysiological systems (MPS) hold promise for a new paradigm in early GI safety assessment during drug discovery.
- * Further development aligned with drug discovery needs is crucial for the widespread adoption of MPS for DI-GIT assessment.
