Receptor-mediated transport of therapeutics across the blood-brain barrier.
The delivery of nonlipophilic compounds to the brain is severely hindered by the blood-brain barrier (BBB). However, brain capillary endothelial cells, which form the BBB, do possess specific receptor-mediated transport mechanisms that potentially can be exploited as a means to transport therapeutic molecules to the brain. We have found that antibodies that bind to the transferrin receptor selectively target BBB endothelium, are transported into the brain, and can function as carriers for the delivery of compounds, including proteins, to the central nervous system. This drug delivery system has been used to transport nerve growth factor across the BBB in a biologically active form and at levels sufficient to prevent the degeneration of nerve growth factor-dependent neurons.
Friden
P M
PM
Alkermes, Inc., Cambridge, Massachusetts.
D000818:Animals; D001666:Binding Sites, Antibody / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006801:Humans; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009474:Neurons / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage / Q000493:pharmacokinetics
D002352:Carrier Proteins; D009414:Nerve Growth Factors; D011990:Receptors, Transferrin; D014660:Vasoactive Intestinal Peptide