Development of a Gastrointestinal Tract Microscale Cell Culture Analog to Predict Drug Transport

Abstract

Microscale cell culture analogs (μCCAs) 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 μCCA to a multi-chamber chip μCCA representing the primary circulation. The GI tract μCCA 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 μCCA. The chip and GI tract μCCAs have been used to recreate the toxic effects of acetaminophen. Preliminary results have shown that the GI tract μCCA acts as a barrier to drugs entering the chip, mimicking in vivo function in this regard.