期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 148, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ejps.2020.105314
关键词
Blood-brain barrier; Transferrin receptors; Solid lipid nanoparticles (SLN); Nanostructured lipid carriers (NLC); Amyloid-beta peptide
资金
- European Union (FEDER funds)
- National Funds (FCT/MEC, Fundacao para a Ciencia e a Tecnologia and Ministerio da Educacao e Ciencia) under the partnership agreement PT2020 [UID/QUI/50006/2013 -POCI/01/0145/FEDER/007265]
- FCT/MCTES (PIDDAC) [UID/EQU/00511/2019]
- FEDER funds through COMPETE2020-Programa Operacional Competitividade e Internacionalizacao (POCI) [POCI-01-0145-FEDER-006939]
- national funds (PIDDAC) through FCT/MCTES [POCI-01-0145-FEDER-006939]
- Norte Portugal Regional Operational Programme (NORTE 2020), under PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) [NORTE-01-0145-FEDER-000005]
- ARDITI [ARDITICQM_2017_011-PDG, M1420-01-0145-FEDER000005-CQM+]
- CQM strategic program [PEst-OE/QUI/UI0674/2019]
- FCT [SFRH/BD/130147/2017]
- [NORTE-01-0145-FEDER-000011]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/130147/2017] Funding Source: FCT
Quercetin was encapsulated in lipid nanoparticles (SLN and NLC) to take advantage of its neuroprotective properties in Alzheimer's disease. The nanoparticles were functionalized with transferrin to facilitate the passage across the blood-brain barrier through the transferrin receptors overexpressed in brain endothelial cells. NMR and FTIR confirmed the functionalization of the nanoparticles with transferrin. TEM results showed all nanoparticles presented spherical morphology. Nanoparticles exhibited size around 200 nm and zeta potential values higher than -30 mV. Quercetin entrapment efficiency was around 80-90%. LDH cytotoxicity assays in hCMEC/D3 cell line demonstrated that even for the highest concentration (30 mu M) nanoparticles did not reveal cytotoxicity after 4 h of incubation. Permeability studies across hCMEC/D3 cell monolayers showed NLC permeate more the blood-brain barrier, while amyloid-beta studies demonstrated NLC-transferrin have the capacity to inhibit fibril formation. Nanoparticles seem to be suitable for brain applications, mainly for Alzheimer's disease due to inhibition of amyloid-beta aggregation.
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