title: Drug targeting to the brain.
abstract: The goal of brain drug targeting technology is the delivery of therapeutics across the blood-brain barrier (BBB), including the human BBB. This is accomplished by re-engineering pharmaceuticals to cross the BBB via specific endogenous transporters localized within the brain capillary endothelium. Certain endogenous peptides, such as insulin or transferrin, undergo receptor-mediated transport (RMT) across the BBB in vivo. In addition, peptidomimetic monoclonal antibodies (MAb) may also cross the BBB via RMT on the endogenous transporters. The MAb may be used as a molecular Trojan horse to ferry across the BBB large molecule pharmaceuticals, including recombinant proteins, antibodies, RNA interference drugs, or non-viral gene medicines. Fusion proteins of the molecular Trojan horse and either neurotrophins or single chain Fv antibodies have been genetically engineered. The fusion proteins retain bi-functional properties, and both bind the BBB receptor, to trigger transport into brain, and bind the cognate receptor inside brain to induce the pharmacologic effect. Trojan horse liposome technology enables the brain targeting of non-viral plasmid DNA. Molecular Trojan horses may be formulated with fusion protein technology, avidin-biotin technology, or Trojan horse liposomes to target to brain virtually any large molecule pharmaceutical.
authors.affiliation: Department of Medicine, UCLA, Warren Hall 13-164 900 Veteran Ave, Los Angeles, CA 90024, USA. wpardridge@mednet.ucla.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Pardridge
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D008969:Molecular Sequence Data; D010957:Plasmids; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D000911:Antibodies, Monoclonal; D008081:Liposomes; D011994:Recombinant Proteins