期刊
NANOTECHNOLOGY
卷 26, 期 49, 页码 -出版社
IOP PUBLISHING LTD
DOI: 10.1088/0957-4484/26/49/495103
关键词
blood-brain barrier; drug-delivery; nanotechnology; solid lipid nanoparticles; active-targeting; functionalization; apolipoprotein E
资金
- National Funds (FCT, Fundacao para a Ciencia e a Tecnologia) [Pest-C/EQB/LA0006/2013]
- European Union (FEDER funds) [NORTE-07-0124-FEDER-000067]
- FCT [SFRH/BD/73379/2010]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/73379/2010] Funding Source: FCT
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.
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