title: Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood-brain barrier (BBB).
abstract: Human serum albumin (HSA) nanoparticles were manufactured by desolvation. Transferrin or transferrin receptor monoclonal antibodies (OX26 or R17217) were covalently coupled to the HSA nanoparticles using the NHS-PEG-MAL-5000 crosslinker. Loperamide was used as a model drug since it normally does not cross the blood-brain barrier (BBB) and was bound to the nanoparticles by adsorption. Loperamide-loaded HSA nanoparticles with covalently bound transferrin or the OX26 or R17217 antibodies induced significant anti-nociceptive effects in the tail-flick test in ICR (CD-1) mice after intravenous injection, demonstrating that transferrin or these antibodies covalently coupled to HSA nanoparticles are able to transport loperamide and possibly other drugs across the BBB. Control loperamide-loaded HSA nanoparticles with IgG2a antibodies yielded only marginal effects.
authors.affiliation: Institute for Pharmaceutical Technology, Goethe-University, Frankfurt, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Telli
authors.initials: T
authors.lastname: Hekmatara
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Herbert
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008139:Loperamide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles; D010146:Pain / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry; D011990:Receptors, Transferrin / Q000276:immunology; D012709:Serum Albumin / Q000737:chemistry; D014168:Transferrin / Q000737:chemistry
chemical_list: D000700:Analgesics; D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D011990:Receptors, Transferrin; D012709:Serum Albumin; D014168:Transferrin; D011092:Polyethylene Glycols; D008139:Loperamide