Preliminary studies of oral mucosal delivery of peptide drugs

Abstract

For chronic therapy involving peptide drugs, delivery across mucosal epithelia is a desirable alternative to a parenteral route of administration. Among the various absorptive mucosae, the nasal area has received considerable attention in the past few years and, to a lesser extent, the rectal region has also been studied. An oral route, however, would offer certain advantages in terms of patient acceptance over the nasal and rectal routes, and our laboratory has recently begun an investigation of the buccal epithelium as a potential oral route of peptide delivery. In addition to its known absorptive capability, this epithelium is attractive because it is “accessible”, in terms of location, to both the researcher and patient, the environment of the drug delivery system is more easily controlled, and polymer technology is available to make buccal patches that are both acceptable to the patient and compatible with the drug and associated additives. Preliminary experiments in our laboratory were conducted in order to address three aspects relative to buccal delivery of peptides: a) Assessment of the hamster cheek pouch as a potential model for buccal absorption, b) Development of an in vivo perfusion model in dogs for the purpose of investigating epithelial permeability and potential methods of permeability enhancement. Such perfusion apparatus has considerable constraints in terms of not disrupting the normal tissue and supratissue environment but yet being able to be used in a fully awake animal, c) Development of a sustained release bioadhesive patch to demonstrate the principle of localization of a peptide delivery system in a selected region of the GI tract. The patch must remain in place for the better part of a day, under varying conditions of food and beverage intake, and be biocompatible with the underlying tissue. In vitro permeability studies of water, butanol, and a representitive peptide through oral mucosa from hamster and dog reveal similar permeability characteristics for these tissues. An in vivo buccal perfusion study in dogs using the peptide was conducted. Comparison of plasma levels from buccal delivery versus I. V. infusion confirm that the buccal route has substantial potential for administration of peptides.