Enzymatic barriers to peptide and protein absorption.

Continuing advances in biotechnology promise to provide a large number of peptides and proteins that would significantly expand the range of pharmaceuticals to treat diseases now poorly controlled. Even at this early stage, it is clear that the success of these entities as drugs of the future would depend, at least in part, on the success in overcoming the obstacles in their delivery. Chief among these are the ubiquitous enzymatic barriers. These include the site of administration, where the peptide is placed, the vascular endothelium that peptides must cross to enter the circulation, the blood that distributes the peptide to its target site, and the liver and kidneys where the peptide is metabolized and eliminated, respectively. The review examines: (1) the nature and efficiency of the enzymatic barriers in degrading peptides and proteins at various absorption sites, and (2) the strategies that can be used to perturb these barriers. These sites include the subcutaneous and intramuscular spaces and the intestinal, nasal, buccal, rectal, vaginal, and ocular surfaces.