Chimeric peptides for neuropeptide delivery through the blood-brain barrier
AssigneeThe Regents of the University of California
InventorWilliam M. Pardridge
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Abstract
Chimeric peptides adapted for delivering neuropharmaceutical agents, such as neuropeptides into the brain by receptor-mediated transcytosis through the blood-brain barrier. The chimeric peptides include a peptide which by itself is capable of crossing the blood-brain barrier by transcytosis at a relatively high rate. The transportable peptide is conjugated to a hydrophilic neuropeptide which by itself is transportable only at a very low rate into the brain across the blood-brain barrier. The resulting chimeric peptide is transported into the brain at a much higher rate than the neuropeptide alone to thereby provide an effective means for introducing hydrophilic neuropeptides into the brain through the blood-brain barrier.
Claims19
A chimeric peptide adapted for delivering a neuropharmaceutical agent into the brain by transcytosis through the blood-brain barrier, said chimeric peptide comprising:
- a transportable peptide capable of crossing the blood-brain barrier by transcytosis, said peptide being selected from the group consisting of insulin, transferrin, IGF-I, IGF-II, basic albumin and prolactin;
- and
- a neuropharmaceutical agent selected from the group consisting of somatostatin, thyrotropin releasing hormone, vasopressin, alpha interferon, endorphin, muramyl dipeptide and L-methionyl(sulfone)-L-glutamyl-L-histidyl-L-phenylalanyl-D-lysyl-L-phenyl alanine, wherein said neuropharmaceutical agent is conjugated with said transportable peptide.
A method for delivering a neuropharmaceutical agent into the brain of an animal by transcytosis through the blood-brain barrier comprising the step of introducing a chimeric peptide into the bloodstream of said animal in a sufficient amount to provide transport of said chimeric peptide across said blood-brain barrier, wherein said chimeric peptide comprises a transportable peptide capable of crossing the blood-brain barrier conjugated with a neuropharmaceutical agent.
In a method for introducing a neuropharmaceutical agent into the brain across the blood-brain barrier, wherein the improvement comprises increasing the rate at which said neuropharmaceutical agent crosses the blood-brain barrier by conjugating said neuropharmaceutical agent with a transportable peptide capable of crossing the blood-brain carrier by transcytosis.
Dependencies are inferred from the claim text.