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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2015

Autores

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

Revista

Título: Nanotechnology

Vol. 26

Página Final: 495103

ISSN: 0957-4484

Editora: Institute of Physics Publishing

Indexação

ISI Web of Knowledge - 52 Citações

Scopus - 7 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 11