VECTOR-MEDIATED PEPTIDE DRUG-DELIVERY TO THE BRAIN

Peptides are potential new CNS pharmaceuticals should these highly water soluble compounds be made transportable through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo. One strategy for peptide drug delivery to the brain is the use of chimeric peptides. The latter are formed when a transportable vector, such as cationized albumin or a receptor-specific monoclonal antibody, is conjugated to a therapeutic compound that is normally not transported through the BBB. The conjugation of drugs to transport vectors is facilitated by the use of avidin-biotin technology. Existing transport vectors achieve degrees of brain delivery that are approximately 40-fold greater than the brain delivery of morphine, a neuroactive small molecule. Ongoing brain vector discovery programs may lead to new vectors with higher degrees of activity and brain specificity. The chimeric peptide approach to brain drug delivery is an advanced technology that requires integrated progress in three inter-dependent spheres: the vector sphere, the linker sphere, and the drug activity sphere. The complexities of the chimeric peptide technology illustrate the importance of integrating CNS drug discovery and CNS drug delivery as early as possible in the overall brain drug development process.