A. Burkhart, M. Azizi, M.S. Thomsen, L.B. Thomsen and T. Moos Pages 4092 - 4099 ( 8 )
The blood-brain barrier (BBB), formed by brain capillary endothelial cells, prevents the entry of several drug molecules to the brain, especially molecules hydrophilic in nature. Advanced drug carriers like nanoparticles share the potential to allow entry of therapeutic proteins and genetic molecules into the central nervous system (CNS). Taking a targeting approach by conjugating molecules acting as ligands or monoclonal antibodies with affinity for proteins expressed on the luminal side of brain capillary endothelial cells, the nanoparticles can be designed to enable transport into the brain endothelium, or perhaps even through the endothelium leading to blood to brain transport. Currently, the iron-binding protein transferrin or antibodies raised against the transferrin receptor denote the most feasible molecule for targeting purposes at the BBB. This manuscript reviews the targetability of nanoparticles to the brain capillary endothelial cells, how nanocarriers may enter and transfer through the brain endothelium, and how likely restraints denoted by the threedimensional mesh of the extracellular proteins forming the brain capillary basement membrane challenge the possibilities for enabling transport of large molecules through the BBB encapsulated in nanoparticles.
Basement membrane, blood-brain barrier, endocytosis, nanoparticle, neurodegeneration, OX26, transcytosis, transferrin.
Laboratory of Neurobiology, Biomedicine Group, Department of Health Science and Technology, Fr. Bajers Vej 3B, 1.216, Aalborg University, DK-9220 Aalborg East, Denmark.