Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 90, Issue 11, Pages 1681-1698Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.1119
Keywords
blood-brain barrier; in vitro model; cell culture; permeability; brain capillary endothelial cell; transendothelial transport
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A relatively simple, widely applicable, and robust in vitro method of predicting blood-brain barrier (BBB) permeability to central nervous system-acting drugs is an increasing need. A cell-based model offers the potential to account for transcellular and paracellular drug diffusional processes, metabolism, and active transport processes, as well as nondefined interactions between a drug and cellular material that may impact upon a membrane's overall permeability profile. Any in vitro BBB cell model to be utilized for the transendothelial BBB permeability screening of potential central nervous system drugs must display reproducible solute permeability, and a number of other general criteria including: a restrictive paracellular barrier; a physiologically realistic cell architecture; the functional expression of key transporter mechanisms; and allow ease of culture to meet the technical and time constraints of a screening program. This article reviews the range of in vitro cell-based BBB models available, including the primary/low passage bovine and porcine brain endothelial cultures as well as the spectrum of immortalized brain endothelial cell lines that have been established. The article further discusses the benefits and limitations of exploiting such systems as in vitro BBB permeability screens. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.
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