Multicompartmental dynamic models for permeability studies

Permeation studies represent a fundamental step in the early stages of drug discovery. In this context, several in vitro preclinical models have been recently developed and optimized to better resemble human physiology in the lab and serve as an animal alternative to accomplish the 3Rs (reduce, refine, replace) principles. However, numerous models are ineffective in recapitulating the dynamic feature of the human barrier tissues, lacking in prediction potential for drug permeation during the preclinical stage. In this book chapter, we provide an overview of the most promising in vitro dynamic models aimed at mimicking the human physiological barriers for pharmaceutical screening, by adopting multicompartmental models. We will present innovative multicompartmental dynamic models currently adopted in different scenario (e.g., lung, intestinal, kidney, and blood–brain barrier) for reproducing the dynamic stimuli to which cells are exposed in the native microenvironment.