Colonic epithelium drug absorption barrier

An increasing number of preclinical and clinical studies have been conducted in recent years aiming to clarify the barrier function of the colonic epithelium in more detail and to devise drug delivery strategies, for example, by modulating factors limiting colonic drug absorption. For preclinical... 

Cell monolayers grown on permeable culture inserts form confluent mono-layers with barrier properties and can be used for drug absorption experiments. The most well-known cell line for the in vitro determination of intestinal drug permeability is the human colon adenocarcinoma Caco-2 [20, 21], The utility of the Caco-2 cell line is due to its spontaneous differentiation to enterocytes under conventional cell culture conditions upon reaching confluency on a porous membrane to resemble the intestinal epithelium. This cell model displays small intestinal carriers, brush borders, villous cell model, tight junctions, and high resistance [22], Caco-2 cells express active transport systems, brush border enzymes, and phase I and II enzymes [22-24], Permeability models... 

The gastrointestinal epithelium forms an extrinsic and an intrinsic barrier against diffusion of toxins and pathogens. The extrinsic barrier is characterized by secretion of mucus, which hinders colonization and accelerates clearance of pathogenic organisms. The importance of mucus as a barrier to drug absorption is discussed in Chapter 2 of this book. In addition, the intestinal immune... 

The rate and extent of intestinal permeation is dependent on the physicochemical properties of the compound (see Sections 16.1.2 and 16.4.3) and the physiological factors. Drugs are mainly absorbed in the small intestine due to its much larger surface area and less tight epithelium in comparison to the colon [17]. The permeation of the intestine may be affected by the presence of an aqueous boundary layer and mucus adjacent to cells, but for a majority of substances the epithelial barrier is the most important barrier to drug absorption. The lipoidal cell membrane restricts the permeability of hydrophilic and charged compounds, whereas large molecules are restricted by the ordered structure of the lipid bilayer. 

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