Enhancement of in vitro permeability of porcine buccal mucosa by bile salts: kinetic and histological studies

Abstract

In this study the enhancing effects of di-and tri-hydroxy bile salts on buccal penetration were investigated using fluorescein isothiocyanate (FITC) as a model permeant. The permeability of the porcine buccal mucosa to this compound in the presence and absence of bile salts was determined in vitro. In conjunction with kinetic studies, histological studies were carried out to investigate the interaction between the bile salts and the buccal epithelium at the light and electron microscopic level. In the presence of the bile salts at 0.l M concentration, the permeability of buccal mucosa to FITC increased by a 100–200 fold compared to FITC alone. Calculation of enhancement ratios provided normalization of the permeability data for the enhancer treated tissue with respect to its own control. No significant difference was observed between the enhancing effects of di-hydroxy and tri-hydroxy bile salts. After the bile salt treatment significant morphological and ultrastructural changes occurred. At LM level, partial loss of superficial cells was observed as well as separation of the epithelium from the basal lamina. Upon a 4 hour bile salt treatment, two important changes were observed with FFEM: (1) the fracture plane preferentially ran across the cytoplasmic proteins and through the cytoplasmic space domains; (2) abnormally structured deposits were found in the cytoplasm. Similar to the kinetic studies, no differences were found between the histological effects of di- and tri-hydroxy bile salts.