Abstract

Prediction of Gastrointestinal Toxicity and Drug Absorption Using the Reconstructed 3D Model of Human Small Intestine Epithelium (EpiIntestinal)

Jan Markus, Production Manager/Senior Scientist, MatTek IVLSL

Small intestine is an important entry gateway for many nutrients, drugs and other substances. About 90% of orally administered drug absorption occurs in the small intestine. Thereby there is a need of good and reliable in vitro model capable to predict drug toxicity and absorption/metabolism patterns that would replace intestine models relying predominantly on the use of cell lines generated from the colon or kidney.

The reconstructed 3D human small intestine model – EpiIntestinal mimics morphology and cell-type composition of normal human small intestine. It is polarized, allows studying bidirectional drug penetration through intestinal wall and expresses proteins involved in active drug transport and metabolism at physiological level. This allows modelling of complex drug absorption profiles, including the permeation, metabolism, drug-drug interaction and adverse effects of drugs on epithelium. Our results revealed that EpiIntestinal mimics the in vivo drug absorption profile much closer than the cancer cell line-based model. EpiIntestinal was also shown to predict toxicity with much higher specificity and sensitivity than the animal model. All in all, this model represents a promising tool to model complex processes occurring in small intestine.