Receptor-Mediated Transport of Drugs Across the BBB

Blood–brain barrier (BBB) limits drug delivery to the brain parenchyma. The ultimate goal of brain drug targeting technology is to deliver therapeutic agents across BBB. Insulin or transferrin as well as other endogenous peptides undergo receptor-mediated transcytosis or transport (RMT) across the BBB in vivo. Certain peptidomimetic monoclonal antibodies (mAb) for insulin receptor or transferrin receptor can also cross the BBB via RMT on the endogenous receptors. These mAb can act as molecular Trojan horses to shuttle into the brain a wide range of therapeutics including recombinant proteins, antibodies, RNA interference drugs, or non-viral gene products. During the last two decades, RMT-based brain drug transport techniques have been developed. This chapter will focus on introducing three major technologies in the arena of RMT brain drug delivery: (1) Avidin–biotin technology; (2) Fusion protein technology; and (3) Trojan horse liposomes (THLs).