Enhancing effect of chitosan on peptide drug delivery across buccal mucosa

The buccal mucosa represents a potentially important topical route for deli very of peptide or protein drugs with some unique advantages such as the av oidance of hepatic first-pass metabolism and the acidity and protease activ ity encountered in the gastrointestinal tract. However, the bioavailabiliti es or relative potencies of intraorally administered peptides are usually q uite low, unless permeabilizers are employed. Chitosan, a mucopolysaccharid e of marine origin, has been claimed to act both as a bioadhesive and perme abilizer, making it a candidate system for mucosal drug delivery. In this s tudy, the enhancement effect of chitosan in gel form for oral mucosa was in vestigated with a large bioactive peptide, transforming growth factor-beta (TGF-beta). Chitosan gel was prepared at 2% concentration in dilute lactic acid and TGF-beta was incorporated into the gel. The effect of chitosan as a permeabilizer was determined by measuring the flux of TGF-beta across por cine oral mucosa in an in vitro system. The localization of TGF-beta within the oral mucosa was determined by horizontal sectioning and counting. Chit osan was found to exert a marked permeabilizing effect on buccal mucosa for peptide drug. (C) 2000 Elsevier Science Ltd. All rights reserved.