Development of a gastrointestinal tract microscale cell culture analog to predict drug transport.

Abstract

Microscale cell culture analogs (microCCAs) are used to study the metabolism and toxicity of a chemical or drug. These in vitro devices are physical replicas of physiologically based pharmacokinetic models that combine microfabrication and cell culture. The goal of this project is to add an independent GI tract microCCA to a multi-chamber chip microCCA representing the primary circulation. The GI tract microCCA consists of two chambers separated by a microporous membrane on which intestinal epithelial cells are cultured. Compounds of interest are pumped through the top chamber, allowing drug to be absorbed through the epithelial layer and circulated into the chip microCCA. The chip and GI tract microCCAs have been used to recreate the toxic effects of acetaminophen. Preliminary results have shown that the GI tract microCCA acts as a barrier to drugs entering the chip, mimicking in vivo function in this regard.