A Comparison of Drug Transport through Cultured Monolayers of Bovine Brain Capillary and Bovine Aortic Endothelial Cells

Abstract

To examine how efficient primary cultured brain capillary endothelial cells are as an in vitro blood-brain barrier (BBB) system with regard to drug transport, we compared bovine brain capillary endothelial cells (BBCEC) with bovine aortic endothelial cells (BAEC). Paracellular and transcellular transport were examined. [14C]Sucrose and fluorescein isothiocyanate-dextran (FITC-dextran)(average molecular weight about 4400 and 71200) were used as indices of paracellular transport. The permeability coefficients of [14C]sucrose and FITC-dextran through BBCEC monolayers were about 3 and 30—40 fold lower than those through BAEC monolayers, respectively. Transcellular transport was examined by means of [3H]leucine and [3H]alanine uptake studies. The Kmvalue (Michaelis constant) of the amino acid uptake was lower in BBCEC than in BAEC. BBCEC had higher alkaline phosphatase (ALP) and y-glutamyl transpeptidase (y-GTP) activity than BAEC when cultured in vitro. These results suggest that BBCEC are suitable for drug transport studies across the BBB in vitro. © 1994, The Pharmaceutical Society of Japan. All rights reserved.