The blood-brain barrier -- the filter that governs what can and cannot come into contact with the mammalian brain -- is a marvel of nature. It effectively separates circulating blood from the fluid that bathes the brain, and it keeps out bacteria, viruses and other agents that could damage it.
The blood-brain barrier depends on the unique qualities of endothelial cells, the cells that make up the lining of blood vessels. In many parts of the body, the endothelial cells that line capillaries are spaced so that substances can pass through. But in the capillaries that lead to the brain, the endothelial cells nestle in tight formation, creating a semi-permeable barrier that allows some substances -- essential nutrients and metabolites -- access to the brain while keeping others -- pathogens and harmful chemicals -- locked out.
This defence is a real headache for treating brain tumours and other neurological conditions. Drugs, treated as foreign molecules by the BBB, are unable to pass.
The biology is really against drug delivery to the brain, so clever strategies are needed,' says Joan Abbott, a neuroscientist at King's College London, UK. 'In the past, big drug companies had simplified things by sticking to small molecules which had the right chemistry and avoided the efflux transporters.' One important recent insight is that increased lipid-solubility is not necessarily better; for most drugs it is the 'free unbound' concentration in the brain that is important, whereas lipophilic drugs tend to stick to other structures inside the brain, including lipid membranes.
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