title: Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E.
abstract: Nanotechnology can be an important tool to improve the permeability of some drugs for the blood-brain barrier. In this work we created a new system to enter the brain by functionalizing solid lipid nanoparticles with apolipoprotein E, aiming to enhance their binding to low-density lipoprotein receptors on the blood-brain barrier endothelial cells. Solid lipid nanoparticles were successfully functionalized with apolipoprotein E using two distinct strategies that took advantage of the strong interaction between biotin and avidin. Transmission electron microscopy images revealed spherical nanoparticles, and dynamic light scattering gave a Z-average under 200 nm, a polydispersity index below 0.2, and a zeta potential between -10 mV and -15 mV. The functionalization of solid lipid nanoparticles with apolipoprotein E was demonstrated by infrared spectroscopy and fluorimetric assays. In vitro cytotoxic effects were evaluated by MTT and LDH assays in the human cerebral microvascular endothelial cells (hCMEC/D3) cell line, a human blood-brain barrier model, and revealed no toxicity up to 1.5 mg ml(-1) over 4 h of incubation. The brain permeability was evaluated in transwell devices with hCMEC/D3 monolayers, and a 1.5-fold increment in barrier transit was verified for functionalized nanoparticles when compared with non-functionalized ones. The results suggested that these novel apolipoprotein E-functionalized nanoparticles resulted in dynamic stable systems capable of being used for an improved and specialized brain delivery of drugs through the blood-brain barrier.
authors.affiliation: 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.initials: AR
authors.lastname: Neves
authors.forename: Joana Fontes
authors.initials: JF
authors.lastname: Queiroz
authors.forename: Babette
authors.initials: B
authors.lastname: Weksler
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Romero
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Couraud
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D001057:Apolipoproteins E / Q000737:chemistry*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*
chemical_list: D001057:Apolipoproteins E; D004337:Drug Carriers