Development of a mucoadhesive and permeation enhancing buccal delivery system for PACAP (pituitary adenylate cyclase-activating polypeptide)

The buccal mucosa providing direct entry into the systemic circulation appears to be a potential site for the delivery of PACAP (pituitary adenylate cyclase-activating polypeptide), a new therapeutic agent in the treatment of type 2 diabetes. In order to reach a sufficient buccal bioavailability a drug delivery system with strong permeation enhancing and mucoadhesive properties is needed. In this study the enhancing effect of a strongly mucoadhesive chitosan-thioglycolic acid (TGA) conjugate in combination with reduced glutathione (GSH) on the permeation of PACAP across the buccal mucosa was investigated. The apparent permeability coefficient (P-app) of PACAP in buffer only was (5.7 +/- 3.1) x 10(-8), while in the presence of chitosan-TGA conjugate (1%) a P-app of (20.0 +/- 3.4) x 10(-8) was achieved. The combination of chitosan-TGA (1%) with GSH (2%) led to an improvement of the P-app up to (57.3 +/- 31.7) x 10(-8). Release studies of PACAP demonstrated that a controlled release can be provided from tablets consisting of chitosan-TGA at a pH of 5, whereas more than twice as much was released from chitosan-TGA tablets pH 4. According to the combination of permeation enhancing properties, controlled drug release and the mucoadhesive character, chitosan TGA conjugates represent a promising tool for the buccal administration of PACAP. (C) 2005 Elsevier B.V. All rights reserved.