Enzymatic Barriers to Peptide and Protein Absorption and the Use of Penetration Enhancers to Modify Absorption
The mammalian body possesses several extremely efficient mechanisms to restrict the entry of macromolecules. These include the presence of various epithelia that are poorly absorptive, the presence of significant levels of enzymatic activity at various locations between the point of entry into the systemic circulation and the target site of a peptide or protein, the availability of multiple enzymes to degrade peptides and proteins at a given location, and varying levels of immunoglobulins to neutralize peptides and proteins both before and after they are absorbed. The inevitable result is that the bioavailability of peptides and proteins is likely to be much less than that for small drug molecules, a factor that must be kept in mind in designing realistic strategies to optimize peptide and protein absorption. These strategies include the co-administration of penetration enhancers to alter membrane permeability, coadministration of inhibitors to restrain the activity of proteolytic enzymes primarily at the absorption site, and the design of analogs that are metabolically stable and which, at the same time, may be more readily absorbed.
KeywordsBile Salt Vasoactive Intestinal Peptide Mixed Micelle Sodium Salicylate Penetration Enhancer
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