Transport Mechanisms of Xenobiotics (Caco-2 Cell Monolayer Model) in Relation to the Biopharmaceutics Classification System (BCS)

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: MUDr. Libuše Smetanová Supervisor: Prof. RNDr. Dr.h.c. Jaroslav Květina, DrSc., FCMA Title of Doctoral Thesis: Transport mechanisms of xenobiotics (Caco-2 cell mono- layer model) in relation to the Biopharmaceutics Classi- fication System (BCS) Current technological levels enable to study transbarrier transports of xenobiotics (including gastrointestinal absorption) on in vitro, in situ and in vivo models. In situ and in vivo approaches enable to assess feedbacks at the organ or whole body level, in in vitro models extra barrier factors are eliminated and the models are aimed at the mechanisms of transport processes. In vitro models for studying of transport mechanisms through the intestinal wall are derived either from cell lines (e.g., Caco-2, MDCK, 2/4/A1 cells) or intestinal tissues (e.g., Ussing chamber). The Caco-2 cell monolayer model is one of the relatively most frequently used in vitro models. Caco-2 cells are a cell line derived from colorectal adenocarcinoma. The main characteristic is their spontaneous differentiation with the creation of a monolayer of fully differentiated and polarized cells showing typical brush border and tight junctions under normal culture..