Understanding and circumventing the blood-brain barrier.
The blood-brain barrier presents a challenging obstacle to effective drug delivery to the central nervous system (CNS). Although biologically intended to protect the brain and spinal cord and provide a very stable fluid environment, the presence of a blood-brain barrier makes treatment of many CNS diseases difficult to achieve, as the required therapies cannot be delivered across the barrier in sufficient quantities or at all. Until relatively recently the blood-brain barrier was viewed largely as a physical barrier to diffusion, and the presence of tight junctions between endothelial cells simply prevented the passive diffusion of solutes from blood into the brain. Recent advances in cell and molecular biology have provided new insights into the function of the blood-brain barrier and it is now appreciated that, in addition to being a physical barrier, it is a complex transport and metabolic barrier and is a highly reactive and dynamic endothelium. Advances in understanding of the cell biology of the blood-brain barrier have opened new avenues and possibilities for improved drug delivery to the CNS. The challenges posed by the blood-brain barrier and the possibilities for overcoming them are reviewed.


CONCLUSIONS
Increased understanding of the molecular biology of the blood-brain barrier is now opening the way for new strategies to deliver drugs to the CNS.
Centre for Neuroscience Research, Kings College London, Guy's Campus, London, UK. david.begley@kcl.ac.uk
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Begley
D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D001927:Brain Diseases / Q000188:drug therapy; D002352:Carrier Proteins / Q000502:physiology; D002463:Cell Membrane Permeability; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D016503:Drug Delivery Systems; D004358:Drug Therapy / Q000379:methods; D006801:Humans; D007278:Injections, Spinal; D008081:Liposomes; D008565:Membrane Proteins / Q000502:physiology; D011355:Prodrugs
D002352:Carrier Proteins; D008081:Liposomes; D008565:Membrane Proteins; D011355:Prodrugs