title: Targeting the insulin receptor: nanoparticles for drug delivery across the blood-brain barrier (BBB).
abstract: Human serum albumin (HSA) nanoparticles (NP) were prepared by desolvation. Insulin or an anti-insulin receptor monoclonal antibody (29B4) were covalently coupled to the HSA NP, using the NHS-PEG-MAL-5000 crosslinker. Loperamide-loaded HSA NP with covalently bound insulin or the 29B4 antibodies induced significant antinociceptive effects in the tail-flick test in ICR (CD-1) mice after intravenous injection, demonstrating that insulin or these antibodies covalently coupled to HSA NP are able to transport loperamide across the blood-brain barrier (BBB) which it normally is unable to cross. Control loperamide-loaded HSA NP with immunoglobulin G antibodies yielded only marginal effects. The loperamide transport across the BBB using the NP with covalently attached insulin could be totally inhibited by the pretreatment with the antibody 29B4.
authors.affiliation: Institute for Pharmaceutical Technology, Goethe-University, Frankfurt, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Ulbrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Knobloch
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D007275:Injections, Intravenous; D007328:Insulin / Q000737:chemistry; D008139:Loperamide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008301:Maleimides / Q000737:chemistry; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000737:chemistry; D011972:Receptor, Insulin / Q000276:immunology / Q000378:metabolism*; D012709:Serum Albumin / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D007328:Insulin; D008301:Maleimides; D012709:Serum Albumin; C043592:maleimide; D011092:Polyethylene Glycols; D008139:Loperamide; D011972:Receptor, Insulin