Duodenum Intestine-Chip For Toxicity Assessment

Gastrointestinal (GI) toxicity stands as one of the most prevalent clinical side effects triggered by therapeutics and other xenobiotics. Enhancing the ability to accurately predict the risk of intestinal toxicity during preclinical drug development holds promise for improving the quality of drug treatments and minimizing unwanted side effects in the clinic.

Here, we review how the Duodenum Intestine-Chip was applied to evaluate the toxicity of indomethacin, a known GI toxicant. The Duodenum Intestine-Chip effectively mimics intestinal tissue and replicates in vivo-like physiology for use in assessing drug safety. The co-culture model incorporates organoid-derived primary epithelial cells and primary human small intestinal microvascular endothelial cells (siHIMECs). Indomethacin safety was assessed across multiple endpoints, including I-FABP accumulation, LDH release, morphology, and barrier function. This technology holds potential for future applications assessing drug absorption, drug-drug interactions, and donor-to-donor variability in patient-derived cells.