Drug delivery through the blood-brain barrier

Specific mechanisms functioning at the blood-brain barrier (BBB) for the permeation of drugs and natural compounds in the blood-to-brain and brain-to-blood directions are described. Various anionic compounds are transported by monocarboxylic acid-specific transporter(s). One such transporter is MCT1, which transports lactic acid, short-chain acids and others. As regards cationic compounds, at least two types of transporter for amines and cationic drugs appear to operate. Relatively small peptides are also transported by carrier-mediated transport mechanisms. Peptides can be delivered into the brain by absorptive-mediated endocytosis (transcytosis), which is specific to positively charged peptides or peptides into which positive charges have been introduced. For more specific delivery into brain, receptor-mediated endocytosis for peptides carrying both BBB-transporting and pharmacologically active moieties is promising. Furthermore, specific drug efflux from the brain mediated by P-glycoprotein is described. The utilization and/or avoidance of these specific mechanisms at the BBB should make it possible to enhance delivery of drugs into the brain, or to decrease the apparent permeability in order to prevent undesirable side effects in the central nervous system.