Nanomedicine Making Headway across the Blood Brain Barrier

Abstract

Nanotechnological advances implemented by nanomedicine have allowed significant development of imaging strategies, therapeutics and theranostics for many severe and life threatening diseases such as brain tumors, Alzheimer’s disease, Parkinson’s disease and other neurological disorders. The Blood-Brain Barrier (BBB) and the Blood-Cerebrospinal Fluid Barrier (BCSF) have hindered the effective delivery of brain imaging agents and therapeutics. However, within the last decade, innovations in the design of nanoparticles are proving to be very exciting. Briefly, the blood brain barrier [1-3] is comprised of brain microvascular endothelial cells that are connected by tight junctions. The tight junctions are composed of transmembrane proteins, often dimers, and further anchored by a protein complex that includes zo-1 and associated proteins. In the human brain, there are approximately 100 billion microvascular capillaries, totaling 400 miles in length (roughly the length of Lake Superior). The tight junctions and some selective metabolic barriers/transporters are responsible for preventing, and/or restricting the passage of most compounds in blood into brain. Very small class of drugs or molecules with high lipid solubility and low molecular weight (<500 Daltons) can only cross the BBB. A limited set of nutrients (certain amino acids or glucose) and a restricted number of macromolecules (transferrin, lactoferrin, insulin) are allowed to enter through a complex set of transporters [3]. Brain endothelial cells also express a multidrug resistance protein (e.g. P-glycoprotein, etc.),