STRUCTURAL REQUIREMENTS FOR INTESTINAL-ABSORPTION OF PEPTIDE DRUGS

The clinical development of orally active peptide drugs has been restr icted by their unfavorable physicochemical characteristics, which limi t their membrane permeation, and their lack of stability against enzym atic degradation. Successful oral delivery of peptides will depend, th erefore, on strategies designed to alter the physicochemical propertie s of these potential drugs, without changing their biological activity , in order to circumvent the barrier properties of the intestinal epit helial cells. This manuscript will focus on the physical and metabolic barrier functions of the intestinal mucosa, the structural features o f peptides which influence their passive diffusion and carrier-mediate d transport, including efflux mechanisms, and various approaches used to prevent enzymatic degradation of the peptides and increase their pe rmeability across the intestinal mucosa.