Recent efforts to overcome the blood-brain barrier for drug delivery

Drug delivery to the brain is a vexing problem. Systemic administration is ineffective because the blood-brain barrier (BBB) excludes the transit of m ost compounds from the vasculature into nervous system tissue. Because the BBB restricts the entry of so many potentially therapeutic molecules, resea rchers have devised numerous strategies for brain drug delivery. The most d irect means of targeting drugs to the brain is to deliver them locally usin g implantable pumps, biodegradable polymers or genetically engineered cells . While these approaches each have some merit, combinations of these techno logies are likely to yield the maximum opportunities for brain targeting. I ndeed, convergent advances in developmental biology, human genomics, tissue and organ reconstruction, drug delivery and materials engineering have all advanced to a remarkably sophisticated level. The intersection of these di sciplines is likely to lead to a revolution in localised brain drug deliver y. Two other approaches which do not depend on invasive neurosurgical proce dures are highlighted here including: pharmacological modulation of the BBB based on stimulating endogenous receptors constitutively expressed on the brain endothelial cells of the BBB; and receptor-mediated transport across the BBB, utilising receptor systems that naturally exist and serve to carry molecules into the brain. The principles, issues and progress underlying t hese approaches are discussed with emphasis on the recent patent literature for each.