Bile salts are endogenous surfactants which have been extensively studied as permeability enhancers to increase drug transport across various biological barriers such as the intestine, skin and buccal mucosa. However, only a few studies of the blood brain barrier (BBB) have been carried out. Previous animal studies have shown that 12-monoketocholate (MKC), a semisynthetic bile salt, enhanced brain uptake of quinine and increased the activity of morphine and pentobarbital in rat, which was speculated to be due to modulation of BBB permeability. Drug delivery to brain is largely prevented by the BBB with its densely packed lipid bilayers, tight junctions, efflux transporters and minimal endocytotic activity. The aim of this thesis was to study bile salts as permeability enhancers and to investigate the mechanism by which bile salts potentially enhance BBB permeability.

MKC and three natural bile salts, cholate (C), deoxycholate (DC) and taurocholate (TC) were compared for their effects on the biophysical properties and transport characteristics of four different membrane models. From simple to complex, these were phospholipid monolayers, phospholipid bilayers (liposomes)), RBE4 cells (an immortalized rat brain capillary endothelial cell) and the whole animal (rat). The RBE4 cell line was used as a more complex bilayer model with some similarities to in vivo brain endothelium.