An alternative approach based on microfluidics to study drug metabolism and toxicity using liver and intestinal tissue

PhD ceremony: Mr. P.M. van Midwoud, 14.45 uur, Academiegebouw, Broerstraat 5, Groningen

Thesis: An alternative approach based on microfluidics to study drug metabolism and toxicity using liver and intestinal tissue

Promotor(s): prof. G.M.M. Groothuis, prof. E.M.J. Verpoorte

Faculty: Mathematics and Natural Sciences

A new in vitro system has been developed by Paul van Midwoud to study drug metabolism, drug-drug interactions and interorgan communication. As the ultimate goal was a system which mimics the in vivo situation, microfluidics technology has been applied to the study of slices of intact tissue. Slices of the intact organ best resemble the whole organ, and by incubating them under flow conditions in a microfluidics-based in vitro system, a more natural incubation environment can be maintained. Slices were incubated by Van Midwoud in small microchambers with minimum medium volume, which resulted in high concentrations of metabolites and products. In contrast to conventional systems, the tissue slices in his system were continuously exposed to a flow of fresh medium. A stable tissue-slice incubation environment was thus realized with a continuous influx of nutrients and removal of waste products, similar to what occurs in the human body. The outlet flow can also be directed to another chamber containing a tissue slice from a different organ, to determine interorgan interactions. With this system, the interplay between intestinal and liver slices was studied by investigating the regulation of bile-acid synthesis in the liver. It is even possible to incorporate scarce human material into the microchambers to obtain a more accurate prediction of metabolism in man. This new in vitro system should thus enable a reduction in both animal use and the costs of drug development. Moreover, we will gain greater insight into the metabolism and toxic effects of potential drugs in the early stages of drug development.