Transporting therapeutics across the blood-brain barrier.
In 1996, we are half-way through the Decade of the Brain, yet we still have few effective treatments for major disorders of the central nervous system. These include affective disorders, epilepsy, neurodegenerative disorders, brain tumours, infections and HIV encephalopathy; sufferers far outnumber the morbidity of cancer or heart disease. Increased understanding of the pharmacology of the brain and its blood supply, and methods for rational drug design, are leading to potential new drug therapies based on highly specific actions on particular target sites, such as neurotransmitter receptors and uptake systems. These methods are capable of reducing the side effects that are common with more general treatments. However, all these treatments and potential treatments meet a formidable obstacle--the blood-brain barrier. In this article, we review the properties of this barrier that complicate drug delivery to the brain, and some of the most hopeful strategies for overcoming or bypassing the barrier in humans.
Abbott
N J
NJ
Biomedical Sciences Division, King's College London, UK. nj.abbott@kcl.ac.uk
Romero
I A
IA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000187:drug effects; D001927:Brain Diseases / Q000188:drug therapy*; D002352:Carrier Proteins / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D008055:Lipids / Q000494:pharmacology / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D004337:Drug Carriers; D008055:Lipids