Penetration of the blood-brain barrier by peripheral neuropeptides: new approaches to enhancing transport and endogenous expression.

The blood-brain barrier (BBB) is a structural and functional barrier between the interstitial fluid of the brain and the blood; the barrier maintains the precisely controlled biochemical environment that is necessary for neural function. This constellation of endothelial cells, macrophages, pericytes, and astrocytes forms the neurovascular unit which is the structural and functional unit of the blood-brain barrier. Peptides enter and exit the CNS by transport systems expressed by the capillary endothelial cells of the neurovascular unit. Limiting the transport of peptides and proteins into the brain are efflux transporters like P-gp are transmembrane proteins present on the luminal side of the cerebral capillary endothelium and their function is to promote transit and excretion of drugs from the brain to the blood. Nanocarrier systems have been developed to exploit transport systems for enhanced BBB transport. Recent approaches for enhancing endogenous peptide expression are discussed.