RVG29-Functionalized Lipid Nanoparticles for Quercetin Brain Delivery and Alzheimer¿s Disease

• Type: Article in International Scientific Journal
• Date: 2020

Authors

R. G. R. Pinheiro (Author) Other; Andreia Granja (Author) Other; Joana A. Loureiro (Author) FEUP; Marina Pinheiro (Author) Other; Ana Rute Neves (Author) Other; Salette Reis (Author) Other; Maria do Carmo Pereira (Author) FEUP

Journal

Title: Pharmaceutical Research

Vol. 37 No. 7

Pages: 1-12

ISSN: 0724-8741

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-00S-ET8

DOI: 10.1007/s11095-020-02865-1

Abstract (EN): Purpose: Lipid nanoparticles (SLN and NLC) were functionalized with the RVG29 peptide in order to target the brain and increase the neuronal uptake through the nicotinic acetylcholine receptors. These nanosystems were loaded with quercetin to take advantage of its neuroprotective properties mainly for Alzheimer’s disease. Methods: The functionalization of nanoparticles with RVG29 peptide was confirmed by NMR and FTIR. Their morphology was assessed by transmission electron microscopy and nanoparticles size, polydispersity and zeta potential were determined by dynamic light scattering. The in vitro validation tests were conducted in hCMEC/D3 cells, a human blood-brain barrier model and thioflavin T binding assay was conducted to assess the process of amyloid-beta peptide fibrillation typical of Alzheimer’s disease. Results: RVG29-nanoparticles displayed spherical morphology and size below 250 nm, which is compatible with brain applications. Zeta potential values were between −20 and −25 mV. Quercetin entrapment efficiency was generally higher than 80% and NLC nanoparticles were able to encapsulate up to 90%. The LDH assay showed that there is no cytotoxicity in hCMEC/D3 cell line and RVG29-nanoparticles clearly increased in 1.5-fold the permeability across the in vitro model of blood-brain barrier after 4 h of incubation compared with non-functionalized nanoparticles. Finally, this nanosystem was capable of inhibiting amyloid-beta aggregation in thioflavin T binding assay, suggesting its great potential for neuroprotection. Conclusions: RVG29-nanoparticles that simultaneously target the blood-brain barrier and induce neurons protection against amyloid-beta fibrillation proved to be an efficient way of quercetin delivery and a promising strategy for future approaches in Alzheimer’s disease. [Figure not available: see fulltext.]. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12