title: Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain.
abstract: Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.
authors.affiliation: Goethe-University, Institute of Pharmaceutical Technology, 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: Claudia
authors.initials: C
authors.lastname: Büchel
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry*; D001812:Blood-Brain Barrier / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D057507:Mice, 129 Strain; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019108:Tight Junctions / Q000378:metabolism; D013997:Time Factors
chemical_list: D016632:Apolipoprotein A-I; D012709:Serum Albumin