Blood-brain barrier and new approaches to brain drug delivery.
Morbidity caused by brain dysfunction affects more than 50 million persons in the United States. Although new neuropharmaceuticals have the potential for treating specific brain diseases, they may not effectively enter brain from blood. Safe strategies are needed for drug delivery through the brain capillary wall, which makes up the blood-brain barrier in vivo. Two of these strategies are reviewed, as are related new developments in the molecular and cell biology of the brain capillary endothelium. The production of chimeric peptides represents a physiologic-based strategy for drug delivery. It entails the covalent coupling of the neuropharmaceutical to a brain transport vector, allowing transportation through the blood-brain barrier. Another strategy is biochemical opening of the blood-brain barrier: intracarotid leukotriene infusion is a method for selectively increasing blood-brain barrier permeability in brain tumors without affecting barrier permeability in normal brain tissue.
Pardridge
W M
WM
Department of Medicine, UCLA School of Medicine 90024.
Boado
R J
RJ
Black
K L
KL
Cancilla
P A
PA
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D015289:Leukotrienes / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000502:physiology; D010455:Peptides / Q000493:pharmacokinetics*
D004337:Drug Carriers; D015289:Leukotrienes; D009004:Monosaccharide Transport Proteins; D010455:Peptides