Chimeric peptides as a vehicle for peptide pharmaceutical delivery through the blood-brain barrier.
A new strategy for peptide delivery through the brain capillary wall, i.e., the blood-brain barrier (BBB), is the synthesis of chimeric peptides which are formed by the covalent coupling of a non-transportable peptide (e.g., beta-endorphin) to a transportable peptide that undergoes receptor- or absorptive-mediated transcytosis at the BBB. beta-endorphin was covalently coupled via disulfide linkage to cationized albumin (pI greater than or equal to 9) which, owing to it's highly basic charge, undergoes rapid absorptive-mediated transport into brain from blood. The [3H]labeled beta-endorphin-cationized albumin chimera was rapidly taken up by isolated brain capillaries in vitro and by rat brain in vivo; conversely, the BBB uptake of native [3H]beta-endorphin was negligible. The synthesis of chimeric peptides is a new strategy for solving the problem of peptide delivery through the BBB.
D000818:Animals; D001812:Blood-Brain Barrier; D002196:Capillaries / Q000378:metabolism; D002417:Cattle; D002560:Cerebrovascular Circulation; D002678:Chimera; D004304:Dosage Forms; D004723:Endorphins / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000378:metabolism; D001615:beta-Endorphin
D004304:Dosage Forms; D004723:Endorphins; D010455:Peptides; D012709:Serum Albumin; D001615:beta-Endorphin