Bioavailability mucosal barrier

Because most proteins are susceptible to protease degradation and denaturation in biologic fluids, most biopharmaceuticals must be administered by intravenous, intramuscular, or subcutaneous injection (see Table 5.5). High concentrations of proteases are found in the gastrointestinal tract, nasal mucosa, bronchioles, and alveoli, which severely limit the bioavailability of protein pharmaceuticals after oral, intranasal, and inhalation administration. Diffusional barriers to the passage of relatively large macromolecules preclude transdermal and mucosal administration of protein pharmaceuticals. Research is under way to develop methods that will protect protein drugs from proteolysis and improve transmembrane diffusion. 

Considering patient acceptability and ease of administration, there is no doubt that oral administration is the most favored route, even if there have been reports on successful delivery of macromolecular drugs across nonperoral mucosal routes.6 7 Despite such advantages in oral administration, various barriers are encountered in the gastrointestinal (GI) tract that should be surmounted in order to gain sufficient bioavailability of... 

Studies have shown that gastrointestinal mucus presents a physical barrier to the diffusion of small molecules such as urea, benzoic acid, antipyrine, 1-phenylalanine and warfarin as well as to large protein molecules. Similarly, the passive absorption of testosterone was shown to be doubled upon ridding the intestinal epithelial cells of the overlying mucus layer. However, the situation regarding the effect of mucus on oral bioavailability is a complex one for example, it has been shown that drag binding to the mucosal surface is essential to the absorption of barbituric acid derivatives from the rat small intestine. 

Research into new peptide hormone pharmaceuticals continues along several lines. Probably the most active area of research is into alternative delivery methods such as oral, nasal, buccal, transdermal, or pulmonary. All of these alternatives share issues of barrier penetration (whether mucosal or epidermal), protein stability, rate of clearance, and bioavailability. 

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