Drug delivery across the blood-brain barrier

Brain diseases are a leading cause of disability, morbidity, and mortality. However, the treatment of brain diseases (e.g., neurodegenerative diseases, psychiatric disorders, pain, and brain cancers) is hampered by the blood-brain barrier (BBB). The BBB is a unique membranous barrier formed by the endothelial cells of the brain capillaries. This barrier tightly segregates the brain from the circulating blood maintaining a constant internal environment for optimal neuronal function. Despite the relative impermeability of the BBB, the BBB is associated with a number of specific transport processes from blood to brain, primarily aimed at the transport of glucose and amino acids into the brain and is also permeable to some low-molecular-weight lipid molecules. However, in essence, an estimated 95% of drugs are excluded from the brain. To deliver drugs across the BBB and, thus, treat central nervous system disorders, specific delivery approaches must be adopted. The approaches may be divided into four separate categories: (1) direct injection and implantation; (2) a temporary opening of the BBB using chemical means; (3) the modification of drugs to make them either lipophilic or substrates of endogenous transporters; and (4) the use of nanosystems, which may be either plain nanoparticles, nanoparticles decorated with ligands for specific transporters or nanoparticles coated with water-soluble surfactants. An additional area of interest is delivery via the nasal route. Although some of the brain delivery approaches used to date are indeed promising, it is clear that further work is needed in the area of brain medicine development if we are to meet the global demand for these therapies.