Intestinal mucosa apical membrane

Passive transcellular transport across the intestinal epithelium involves three discrete steps (1) uptake across the apical membrane, (2) diffusion through the cytoplasm, and (3) efflux across the basolateral membrane. Occasionally, drug molecules without favorable physicochemical properties traverse the intestinal epithelium using endogenous membrane transporters.6-8 In addition, the intestinal mucosa, with its numerous drug-metabolizing enzymes and efflux transporters, such as P-glycoprotein (Pgp), functions as a biochemical barrier.9... 

The epithelium is supported underneath by lamina propria and a layer of smooth muscle called muscularis mucosa (3-10 cells thick). These three layers, i.e., the epithelium, lamina propria, and muscularis mucosa, together constitute the intestinal mucosa.On the apical surface, the epithelium along with lamina propria projects to form villi. The cell membranes of epithelial cells that comprise the villi contain uniform microvilli, which give the cells a fuzzy border, collectively called a brush border. These structures, although greatly increase the absorptive surface area of the small intestine, provide an additional enzymatic barrier since the intestinal digestive enzymes are contained in the brush border. In addition, on the top of the epithelial layer lies another layer, the UWL, as previously described. The metabolic and biochemical components of the epithelial barrier will be discussed. 

Figure 11.26 A schematic diagram of an apparatus used to obtain estimates of the passive permeability of a drug candidate across the intestinal mucosa using Caco-2 cells. A monolayer of Caco-2 cells is grown on a porous polyethylene terephthalate (PET) membrane (a so-called confluent monolayer of cells that grows only in two dimensions on such a substrate from an initial small inoculation). In the experiment the cells are submerged in Hanks s Balanced Salt Solution (HBSS) buffer (contains Na+, K+, CP, phosphate, glucose, and in some formulations also Ca +, Mg + and S04 ) the Caco-2 cell layer provides the only connection between an apical (donor) reservoir, into which the drug candidate is dosed, and a basolateral (receiver) reservoir. For the assay, aliquots are removed for analysis from the apical reservoir at Omin, and from both reservoirs at 120 min. Reproduced from Van Pelt, Rapid Commun. Mass Spectrom. 17, 1573 (2003), with permission of John Wiley Sons Ltd.

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