New systems for delivery of drugs to the brain in neurological disease.
The restricted or regulated entry of most blood-borne substances into the brain has been recognised for more than a century. The blood-brain barrier (BBB)-shielding function provided by endothelial cells is important in the treatment of neurological diseases because this exclusion of foreign substances also restricts entry of many potentially therapeutic agents into the brain. The recent identification of several neuroactive proteins of potential therapeutic value has highlighted the crucial need for effective and safe transcapillary delivery methods to the brain. One promising method is delivery through brain capillaries by augmentation of pinocytotic vesicles delivery systems that use this cellular mechanism are in development. Recent investigations in animal models show that large molecules of neurotherapeutic potential can be conjugated to peptidomimetic ligands, which bind to selected peptide receptors, and are then internalised and transported in small vesicles across the cytoplasmic brain capillary barrier. These conjugates have been shown to remain functionally active and effective in animal models of neurological disease.
Cornford
Eain M
EM
Department of Neurology and the Brain Research Institute, UCLA, and the Department of Veterans' Affairs, Los Angeles, 90095-1769, USA. cornford@ucla.edu
Cornford
Marcia E
ME
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D001927:Brain Diseases / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000494:pharmacology; D010873:Pinocytosis / Q000187:drug effects / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D008024:Ligands; D008081:Liposomes; D011993:Recombinant Fusion Proteins