Carrier-mediated transport and efflux mechanisms in Caco-2 cells

Abstract Intestinal absorptive cells express a number of carrier systems that are responsible for the absorption of vitamins, bile acids, amino acids, nucleosides and di/tripeptides. The potential exploitability of these transporters for enhancing oral drug absorption is recognized. However, the structural specificities and functionalities of these transporters need to be characterized in greater detail before their exploitation in drug delivery can be realized. The study of intestinal transporters has been difficult because of the fragility and limited viability of intestinal enterocytes. One model system that has been proven to be useful in this type of study is the human colon adenocarcinoma cell line, Caco-2. Caco-2 cells form monolayers of differentiated epithelial cells joined by intercellular tight junctions, which prevent the paracellular diffusion of solutes. Thus, this system provides a selective barrier for modeling structure transport relationships for both passive and carrier mediated transport. In addition, Caco-2 cells express apical efflux mechanism(s), which may play a role in restricting oral drug absorption. Some enzymes and transport systems are expressed to a lesser extent in Caco-2 cells compared to normal enterocytes. This difference may be due to the colonic origin of Caco-2 cells. Thus, it is important to establish that transport proteins expressed by these cells are biochemically and/or functionally similar to the native transporter found in the small intestine. This comparison is important to establish the utility of the Caco-2 cell model for studying intestinal carriers.