LOCALIZATION OF THE PERMEABILITY BARRIER INSIDE PORCINE BUCCAL MUCOSA - A COMBINED INVITRO STUDY OF DRUG PERMEABILITY, ELECTRICAL-RESISTANCE AND TISSUE MORPHOLOGY

In vitro drug transport and morphological studies were performed on porcine buccal mucosa, in order to localize the permeability barrier inside this tissue. As model compounds, two beta-blocking agents (acebutolol and bupranolol) were used with similar pK(a) and molecular weight values, but with varying hydrophilicity. Porcine buccal mucosa was used, from which the connective tissue was removed by mechanical separation. The splitting procedure permitted the use of epithelial tissue layers of different thicknesses for diffusion experiments and measurements of electrical resistance. Both series of experiments showed that the major barrier to drug transport is not the buccal epithelial layer itself, but rather a deeper tissue layer. Morphological data showed that only the least permeable tissue samples, cut at maximal thickness (0.8 mm). included the entire basal lamina. A similar set of experiments has been performed using EDTA-split epithelium. The permeability and electrical resistance of these epithelia were much greater than for dermatomed tissue. Immunofluorescence microscopy revealed that upon EDTA splitting, the basal lamina remained attached to the connective tissue layer. In all experiments, a semiquantitative correlation was observed between permeability and electrical resistance of the buccal mucosa on the one hand and the degree of integrity of the basal lamina on the other. From the data it was concluded that most likely the basal lamina determines buccal permeability.