In Vitro and Ex Vivo Models to Study Molecular Trafficking Across the Human Intestinal Barrier

The intestine is a complex organ whose main functions are food digestion and nutrient absorption. It is therefore of great interest for pharmaceutical research as a preferred route for drug delivery. In vitro intestinal models are valuable tools for the preclinical evaluation of absorption, distribution, metabolism, and excretion of new therapeutic formulations; consequently, several attempts have been made to recreate the human intestine barrier in vitro. The models so far set up were aimed at mimicking specific intestinal features related to the molecules or processes under investigation. Artificial membranes are suitable to study passive absorption; systems based on 2D/3D cell cultures reproduce the transcellular pathway; organs-on-a-chip mimic the in vivo cellular and mechanical complexity, allowing the identification of the multiple factors involved in molecular interactions with the intestinal barrier; and intestine explants replicate in full the native organ under controlled conditions, thus providing the most comprehensive in vitro model. All these models have advantages and disadvantages but all have given important contribution to advance the knowledge on the interaction of drugs, toxins, and xenobiotic with the intestinal barrier.