Organotypic and microphysiological models of liver, gut and kidney for studies of drug metabolism, pharmacokinetics and toxicity

Despite extensive breakthroughs in chemistry, molecular biology and genetics in the last decades the success rates of drug development projects remain low. To improve predictions of clinical efficacy and safety of new compounds a plethora of 3D culture methods of human cells have been developed in which the cultured cells retain physiologically and functionally relevant phenotypes for multiple weeks. Here, we critically review current paradigms for organotypic cultures of human liver, gut and kidney, such as perfused microchips, spheroids and hollow-fiber bioreactors, and discuss their utility for understanding drug pharmacokinetics, metabolism and toxicity. Furthermore, bioprinting and the microfluidic integration of different tissue models to mimic systemic drug effects are highlighted as promising technological trends. In the last part of the review we discuss important consideration regarding the choice of material of culture substratum to limit adverse effects, such as drug absorption while facilitat...