title: Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones.
abstract: The blood-brain barrier (BBB) represents a considerable obstacle to brain entry of the majority of drugs and thus severely restricts the therapy of many serious CNS diseases including brain tumours, brain HIV, Alzheimer and other neurodegenerative diseases. The use of nanoparticles coated with polysorbate 80 or with attached apolipoprotein E has enabled the delivery of drugs across the BBB. However, the mechanism of this enhanced transport is still not fully understood. In this present study, human serum albumin nanoparticles, with covalently bound apolipoprotein E (Apo E) as a targetor as well as without apolipoprotein E, were manufactured and injected intravenously into SV 129 mice. The animals were sacrificed after 15 and 30 min, and their brains were examined by transmission electron microscopy. Only the nanoparticles with covalently bound apolipoprotein E were detected in brain capillary endothelial cells and neurones, whereas no uptake into the brain was detectable with nanoparticles without apolipoprotein E. We have also demonstrated uptake of the albumin/ApoE nanoparticles into mouse endothelial (b.End3) cells in vitro and their intracellular localisation. These findings indicate that nanoparticles with covalently bound apolipoprotein E are taken up into the cerebral endothelium by an endocytic mechanism followed by transcytosis into brain parenchyma.
authors.affiliation: Goethe-University, Institute of Pharmaceutical Technology, Max-von-Laue-Str. 9 (Biozentrum), D-60438 Frankfurt am Main, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Zensi
authors.forename: David
authors.initials: D
authors.lastname: Begley
authors.forename: Charles
authors.initials: C
authors.lastname: Pontikis
authors.forename: Celine
authors.initials: C
authors.lastname: Legros
authors.forename: Larisa
authors.initials: L
authors.lastname: Mihoreanu
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.forename: Claudia
authors.initials: C
authors.lastname: Büchel
authors.forename: Hagen
authors.initials: H
authors.lastname: von Briesen
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000166:cytology / Q000648:ultrastructure; D005260:Female; D005562:Formazans / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000166:cytology / Q000648:ultrastructure; D006801:Humans; D007202:Indicators and Reagents / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000737:chemistry*; D009474:Neurons / Q000378:metabolism*; D010316:Particle Size; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D005562:Formazans; D007202:Indicators and Reagents; D012709:Serum Albumin