BRAIN DRUG-DELIVERY THROUGH THE BLOOD-BRAIN-BARRIER TRANSPORT-SYSTEMS- ATTEMPTED STRATEGIES AND ISSUES

Passage across the blood-brain barrier is often a limiting factor for the delivery of therapeutic agents to the central nervous system. Drug delivery to the brain is thus an important challenge, particularly fo r the treatment of neurodegenerative diseases or cerebral tumours such as glioma. Strategies to target therapeutic agents to the brain inclu de pharmacological modulation of blood-brain barrier permeability, inc reases in the lipophilicity of the compounds, the use of blood-brain b arrier endogenous transporters, and receptor mediated transcytosis thr ough the blood-brain barrier endothelial cells. The use of blood-brain barrier transporters may be suitable for small molecular weight deriv atives analogous to endogenous substrates, but this strategy is render ed difficult by the specificity of these transporters. On the other ha nd, receptor mediated transcytosis is an appealing perspective for bra in delivery in the form of limited amounts of potent macromolecules su ch as neurotrophic factors or DNA. However, this approach is hamper-ed by its very low capacity and the difficulty of engineering biochemica l vectors devoid of recognition by the immune system.