Development of Gut-Mucus Chip for Intestinal Absorption Study

Abstract

The intestinal epithelium is a major barrier through which orally administered drugs must pass. The intestinal mucosa on the epithelium acts as an additional barrier that protects the intestinal cells from foreign substances, thereby interfering with drug delivery. Caco-2 based cell culture model is a standard in vitro model system for testing drug uptake. However, current in vitro models do not reflect the absorption mechanism of drugs accurately due to the absence of the mucus layer. Here, we developed a microfluidic gut-mucus chip using Caco-2 cells coated with mucin protein. It was confirmed that the mucin layer was maintained under flow conditions by Alcian blue/Periodic Acid Schiff (PAS) staining. In addition, the effect of mucosal layer on drug absorption in the flow environment was examined. Mucus-adhesive particles can be useful for delivery of drugs across the intestinal epithelium. We prepared mucus-adhesive and non-adhesive microparticles containing fluorescent molecules and compared the adhesion of these particles in flow condition. Mucus-coated Caco-2 cells provide a more physiologically realistic intestinal epithelial environment to study uptake processes of drugs released from the mucus-adhesive particles. We hope that the gut-mucus chip could potentially be used as novel and more accurate in vitro models of the intestine.