Development of neuropeptide drugs that cross the blood-brain barrier

In recent years, there have been several important advancements in the development of neuropeptide therapeutics. Nevertheless, the targeting of peptide drugs to the CNS remains a formidable obstacle. Delivery of peptide drugs is limited by their poor bioavailability to the brain due to low metabolic stability, high clearance by the liver, and the presence of the blood brain barrier (BBB). Multiple strategies have been devised in an attempt to improve peptide drug delivery to the brain, with variable results. In this review, we discuss several of the strategies that have been used to improve both bioavailability and BBB transport, with an emphasis on antibody based vector delivery, useful for large peptides/small proteins, and glycosylation, useful for small peptides. Further development of these delivery methods may finally enable peptide drugs to be useful for the treatment of neurological disease states.