title: Apo E-Functionalization of Solid Lipid Nanoparticles Enhances Brain Drug Delivery: Uptake Mechanism and Transport Pathways.
abstract: Several strategies have been implemented to enhance brain drug delivery, and herein solid lipid nanoparticles functionalized with apolipoprotein E were tested in hCMEC/D3 cell monolayers. The mean diameter of 160 nm, negative charge of -12 mV, and their lipophilic characteristics make these nanosystems suitable for brain delivery. Confocal images and flow cytometry data showed a cellular uptake increase of 1.8-fold for SLN-Palmitate-ApoE and 1.9-fold for SLN-DSPE-ApoE when compared with the non-functionalized SLNs. Clathrin-mediated endocytosis was distinguished as the preferential internalization pathway involved in cellular uptake and nanoparticles could cross the blood-brain barrier predominantly by a transcellular pathway. The understanding of the mechanisms involved in the transport of these nanosystems through the blood-brain barrier may potentiate their application on brain drug delivery.
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Ana Rute
authors.identifier: 0000-0003-4262-5837
authors.initials: AR
authors.lastname: Neves
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Joana Fontes
authors.initials: JF
authors.lastname: Queiroz
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Sofia A Costa
authors.identifier: 0000-0001-8777-5877
authors.initials: SAC
authors.lastname: Lima
authors.affiliation: UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto , Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
authors.forename: Salette
authors.identifier: 0000-0002-0736-2835
authors.initials: S
authors.lastname: Reis
mesh_terms: D001057:Apolipoproteins E / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D004337:Drug Carriers / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D004337:Drug Carriers; D008055:Lipids; D010168:Palmitates; D010714:Phosphatidylethanolamines; C038089:1,2-distearoylphosphatidylethanolamine