Novel Organ-on-a-Chip device for high throughput drug candidate screening

Abstract

Organ-on-a-Chip microreactors are in vitro microfluidic devices capable of modelling the function of individual organs of a living organism. The developed Liver-on-a-chip device models certain aspects of liver metabolism. One of the important steps of pharmacokinetic studies related to the preclinical phase of drug research is the in vitro modelling of the liver-bound metabolism of candidate molecules. Drug metabolism in the living organism usually occurs by oxidative transformation catalysed by the cytochrome P450 (CyP450) family of enzymes, which are present in larger quantities in the liver. In the practice of (industrial) pharmaceutical research, a biological model based on liver microsomes (endoplasmic reticulum of hepatocytes) containing the above enzyme is used, but this system has many known limitations. As part of our research, we are developing a new nanocomposite system that is a biomimetic alternative to the currently used in vitro biological model. In the biomimetic system, instead of a liver microsome, we use a metalloporphyrin organocatalyst system immobilised on a nanoparticle and embedded in a polymer nanofiber, which, as a structural analogue of the active site of the CyP450 enzyme family, models the transformation carried out by the microsome, and a potential device for cheap, high throughput metabolite screening.