VISUALIZATION OF ENHANCING EFFECTS OF BILE-SALTS ON BUCCAL PENETRATION

The enhancing effects of bile salts on buccal penetration was investig ated in vitro using porcine buccal mucosa, correlating permeability ch anges with histological effects. The permeability of the buccal mucosa to the model compound fluorescein isothiocyanate (FITC) was studied i n the presence and absence of bile salts. Light microscopy, freeze-fra cture electron microscopy and confocal laser scanning microscopy were used in order to investigate the interaction between the bile salts an d the buccal epithelium. A significant increase in permeation of FITC was obtained after coadministration with bile salts. After 4h treatmen t, bile salts (at a concentration of 0.1M) caused a loss of distal lay ers in the epithelium and a split of the epithelium from the connectiv e tissue. The results of freeze-fracture studies show that the bile sa lts affect the cytoplasmic domain of the buccal epithelium. Due to the bile salt treatment, the mode of fracture was altered in such a way t hat cell membranes were almost absent. However, no differences were ob served between the enhancing effects of dihydroxy and trihydroxy bile salts, either with the transport rate or with the histological studies .