Relationship of octanol/buffer and octanol/water partition coefficients to transcellular diffusion across brain microvessel endothelial cell monolayers

Abstract

The importance of lipid solubility on the rate of passage of solutes across the bovine blood-brain barrier (BBB) was studied with an in vitro BBB model. The model consisted of primary cultured bovine brain microvessel endothelial cell monolayers mounted in a side-by-side diffusion cell. Nine compounds (sucrose, mannitol, urea, glycerol, butyrate, thiourea, caffeine, antipyrine, propanolol) with different octanol/water partition coefficients were selected in order to provide a wide range of lipid solubility. Time- and concentration-dependence, and the effect of bovine serum albumin on the rate of transport of these compounds across the monolayers was determined. Consistent with in vivo studies, a significant positive correlation between transcellular diffusion and octanol/buffer or octanol/water partition coefficients was observed. The passage of these compounds across the monolayers was also concentration-dependent, non-saturable, and reduced in the presence of bovine serum albumin. Results demonstrate that these compounds undergo passive diffusion across the monolayers in which the rate of transfer across the monolayers depends directly on their lipid solubility and indirectly upon molecular size. In addition, serum albumin is an apparent factor in determining the passive permeability of the monolayers.