Solid lipid nanoparticles as a vehicle for brain-targeted drug delivery: two new strategies of functionalization with apolipoprotein E

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Neves, AR (Author) Other; Queiroz, JF (Author) Other; Weksler, B (Author) Other; Romero, IA (Author) Other; Couraud, PO (Author) Other; Salette Reis (Author) FFUP

Journal

Title: Nanotechnology

Vol. 26

Final page: 495103

ISSN: 0957-4484

Publisher: Institute of Physics Publishing

Indexing

ISI Web of Knowledge - 52 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-00G-WXN

DOI: 10.1088/0957-4484/26/49/495103

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11