PEPTIDE DELIVERY INTO THE CENTRAL-NERVOUS-SYSTEM - INVASIVE, PHYSIOLOGICAL AND CHEMICAL APPROACHES

The capillary endothelium of the brain and spinal cord possesses tight junctions and, thus, behaves as a continuous lipid bilayer that preve nts the passage of highly polar and lipid-insoluble substances. Highly active enzymes expressed in the brain endothelial cells and cerebral pericytes also represent a metabolic component that contributes to the homeostatic balance of the central nervous system (CNS). Peptides can not enter the brain and spinal cord from the circulating blood because they are highly polar and lipid insoluble, metabolically unstable, an d generally do not have active transport systems in this membranous ba rrier. Hence, the blood-brain barrier (BBB) is the major obstacle to p eptide-based therapeutics that are potentially useful for combating di seases affecting the central nervous system. The article discusses inv asive, physiological-based and chemical-enzymatic approaches to overco me the BBB by reviewing both primary and patent literature.