Abstract

Systematic Investigation of the Effect of Shear Stress in a Microfluidic Intestine-on-a-Chip Model to study oral delivery of vaccines

Ludivine Delon, PhD candidate, Future Industries Institute, University of South Australia

Particulate carriers can protect their biological payloads from the harsh environment of the gastrointestinal tract and have high potential to enhance oral peptide/protein absorption. However, transport through the intestinal epithelium is suboptimal. Current animal and in vitro Transwell models typically fail to reliably predict the uptake of orally administered drugs and vaccines. Indeed, these models only poorly mimic the intestinal epithelium and provide limited mechanistic insights. The integration of microfluidics with living biological systems has paved the way to the exciting concept of “gut-on-a-chip”. However, the optimal mechanical conditions needed to grow intestinal cells in a microfluidic device have not been investigated. To this end, a microfluidic device was developed to create, within a single device, a range of shear stresses physiologically relevant to the intestinal epithelium. This allowed for systematic investigation of the effect of fluid shear on the key characteristics of Caco-2 monolayers. The structural and functional differentiation of the enterocyte monolayer in the chamber was studied using confocal and digital holographic microscopies, mitochondrial mass and the expression of tight junctions, F-actin, microvilli, mucus, drug transport enzyme. Building on this study, intestine-on-chips were developed to systematically investigate the transport of particulate silica carriers.