[Methodologies for regulation of intestinal absorption of biologically active peptides]

Oral bioavailability of biologically active peptides and proteins is generally very low because they are extensively degraded by peptidases and proteases in the gastrointestinal tract and impermeable through the intestinal mucosal membrane. Consequently, although clinical application of peptide drugs is limited to administration by injection, such frequent subjects the patients to considerable pain, and there is also possibility of the manifestation of serious side effects. Therefore various approaches have been examined to overcome the delivery problems of peptide drugs. These approaches include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to modify the peptide molecules to produce prodrugs and analogs, (3) to develop an administration method for peptides that can serve as an alternative to oral and injection administration and (4) to use the dosage forms to these peptide drugs. In this paper, we introduce the approaches (1)-(3) and demonstrate that transmucosal absorption of various biologically active peptides and proteins could be improved by using these approaches. These approaches therefore may give us basic information to improve the intestinal absorption of peptide and protein drugs.