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Peptide and protein drugs are becoming a very important class of therapeutic agents. However, the oral bioavailability of peptide and protein drugs is generally poor because they are extensively degraded by proteases in the gastrointestinal tract or impermeable through the intestinal mucosa. For the systemic delivery of the peptide and protein drugs, parenteral administration is currently required to achieve their therapeutic activities. However, this administration is poorly accepted by patients and may cause allergic reactions and serious side effects. Therefore, various approaches have been examined to overcome the delivery problems of these peptides when they are administered into the gastrointestinal tract and other mucosal sites. These approaches include (1) to use additives such as absorption enhancers and protease inhibitors, (2) to develop an administration method for peptides that can serve as an alternative to oral and injection administration, (3) to modify the molecular structure of peptide and protein drugs to produce prodrugs and analogues, and (4) to use the dosage forms to these peptide drugs. In this study, we demonstrated that the transmucosal absorption of various peptides including insulin, calcitonin, tetragastrin and thyrotropin releasing hormone (TRH) could be improved by the use of these approaches. Therefore, these approaches may give us basic information to improve the transmucosal absorption of peptide and protein drugs.

Improvement of Transmucosal Absorption of Biologically Active Peptide Drugs