Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E. (17th November 2015)

• Record Type: Journal Article
• Authors: Neves, Ana Rute; Queiroz, Joana Fontes; Weksler, Babette; Romero, Ignacio A; Couraud, Pierre-Olivier; Reis, Salette
• Is Part Of: Nanotechnology. Volume 26:Number 49(2015)
• Publication Date: 2015-11-17
• Subjects: blood-brain barrier -- drug-delivery -- nanotechnology -- solid lipid nanoparticles -- active-targeting -- functionalization -- apolipoprotein E; Nanotechnology -- Periodicals; Nanotechnology -- Periodicals; Nanotechnology; Publications périodiques; Nanotechnologies; Periodicals; 620.5
• DOI: 10.1088/0957-4484/26/49/495103
• Languages: English
• ISSNs: 0957-4484

Abstract

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.