Targeting the insulin receptor: nanoparticles for drug delivery across the blood-brain barrier (BBB).
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.
Ulbrich
Karsten
K
Institute for Pharmaceutical Technology, Goethe-University, Frankfurt, Germany.
Knobloch
Thomas
T
Kreuter
Jörg
J
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
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