Other Permeability Barriers in the Buccal Mucosa

In addition to the intercellular lipids of the buccal mucosa, there appear to be other barriers which may reduce the ability of an exogenous compound to permeate the buccal mucosa. These include the salivary film and mucus layer, the basement membrane, and a metabolic barrier. 

Unlike the skin, the mucosae of the oral cavity are constantly maintained moist by the continual secretion of saliva from the three major salivary glands (submandibular, parotid, and sublingual) and the minor salivary glands located in or beneath the mucosae. The thickness of the salivary film (pellicle) has been calculated to be between 70 /rm and 100 /./m [23] however, both the composition and amount of saliva produced can vary between individuals, with time of day, disease states, and drug therapy [33], all of which must be taken into account when considering the oral cavity as a site for drug delivery. 

The function of the mucosal pellicle is to serve as a barrier between the oral epithelial surface and the external environment, and so it may also act as a barrier to drug delivery. However, there are limited studies assessing the role of the mucus layer in buccal permeability. In one study, treatment of the oral mucosa with anticholinergic agents resulted in an increased permeability of certain compounds, and it was suggested that the reduced salivary flow may have been responsible for the reduced barrier properties of the tissue [113]. In 

A recent study, however, has shown that aminopeptidase activity is present on the surface of porcine buccal mucosa, and that various aminopeptidase inhibitors, including amastatin and sodium deoxycholate, reduce the mucosal surface degradation of the aminopeptidase substrate, leucine-enkephalin [149], Since the peptidases are present on the surface of the buccal mucosa, they may act as a significant barrier to the permeability of compounds which are substrates for the enzyme. In addition to proteolytic enzymes, there exist some esterases, oxidases, and reductases originating from buccal epithelial cells, as well as phosphatases and carbohydrases present in saliva [154], all of which may potentially be involved in the metabolism of topically applied compounds. 

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