Over the last decade, there has been a particular interest in delivering drugs, especially peptides and proteins via the buccal route. It provides direct entry into the systemic circulation thus avoiding the hepatic first-pass effect and degradation in the gastrointestinal tract, ease of administration, and the ability to terminate delivery when required. However membrane permeation can be a limiting factor for many drugs administered via the buccal route, and the epithelium that lines the oral mucosa is a very effective barrier to the absorption of drugs. In order to deliver broader classes of drugs across the buccal mucosa, reversible methods of reducing the barrier potential of this tissue must be employed. This requisite has fostered the study of penetration enhancers that will safely alter the permeability restrictions of the buccal mucosa, It has been shown that buccal penetration can be improved by using various classes of transmucosal and transdermal penetration enhancers such as bile salts, surfactants, fatty acids and derivatives, chelators, cyclodextrins and chitosan. Among these chemicals used for the drug permeation enhancement, bile salts are most common. The first parr of this paper focuses on work related to the elucidation of mechanisms of action of bile salts in buccal permeation enhancement of various drugs and mucosal irritation, In the second part, results showing the enhancing effect of chitosan on buccal permeation of hydrocortisone, a commonly used topical oral anti-inflammatory agent, and transforming growth factor beta (TGF-beta), which is a bioactive peptide to which the oral mucosa is relatively impermeable is presented. (C) 2001 Elsevier Science B.V. All rights reserved.