An in vitro mucosal model predictive of bioadhesive agents in the oral cavity

The formulation of a drug/carrier complex that can be distributed and retai ned for extended periods within the oral cavity would be advantageous in th e treatment of local conditions. In this study, an in vitro system was deve loped to investigate the binding of bioadhesive macromolecules to buccal ep ithelial cells, without having to alter their physicochemical properties by the addition of 'marker' entities. In this innovative approach a lectin bi nding inhibition technique, involving an avidin-biotin complex and a colour metric detection system, was used to evaluate polymer binding. 0.5% w/v pol ymer solutions in saline (pH 7.6) were left in contact with a standardized number of freshly collected human buccal cells for 15 min. The cells were t hen exposed to 10 mg L-1 biotinylated lectin from Canavalia ensiformis foll owed by 5 mg L-1 streptavidin peroxidase. The inhibition of lectin binding (i.e. by 'masking' of the binding site on the cell surface by the attached bioadhesive polymer) was measured and expressed as a percentage reduction i n the rate of o-phenylenediamine oxidation over 1 min. From the wide range of polymer solutions screened, chitosan gave the greatest inhibition of lec tin binding to the surface of buccal cells, while methylcellulose, gelatin, Carbopol 934P and polycarbophil also produced a substantial reduction. Lec tin binding inhibition was also observed for a selected number of polymer s olutions when screened at pH 6.2. The presence of bound chitosan, polycarbo phil and Carbopol 934P on the buccal cell surface was confirmed using direc t staining techniques. It was concluded that this assay can be used to dete ct polymer binding to the cells present on the buccal mucosa, and the infor mation gained used in the development of retentive drug/polymer formulation s. (C) 1999 Elsevier Science B.V. All rights reserved.