ENHANCEMENT OF IN-VITRO PERMEABILITY OF PORCINE BUCCAL MUCOSA BY BILE-SALTS - KINETIC AND HISTOLOGICAL STUDIES

In this study the enhancing effects of di-and tri-hydroxy bile salts o n buccal penetration were investigated using fluorescein isothiocyanat e (FITC) as a model permeant. The permeability of the porcine buccal m ucosa to this compound in the presence and absence of bile salts was d etermined in vitro. In conjunction with kinetic studies, histological studies were carried out to investigate the interaction between the bi le salts and the buccal epithelium at the light and electron microscop ic level. In the presence of the bile salts at 0.1 M concentration, th e permeability of buccal mucosa to FITC increased by a 100-200 fold co mpared to FITC alone. Calculation of enhancement ratios provided norma lization of the permeability data for the enhancer treated tissue with respect to its own control. No significant difference was observed be tween the enhancing effects of di-hydroxy and tri-hydroxy bile salts. After the bile salt treatment significant morphological and ultrastruc tural changes occurred. At LM level, partial loss of superficial cells was observed as well as separation of the epithelium from the basal l amina. Upon a 4 hour bile salt treatment, two important changes were o bserved with FFEM: (1) the fracture plane preferentially ran across th e 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 histologic al effects of di- and tri-hydroxy bile salts.