Quercetin lipid nanoparticles functionalized with transferrin for Alzheimer's disease

•Quercetin-loaded lipid nanoparticle functionalized with transferrin was developed.•No cytotoxicity of nanoparticles was detected in hCMEC/D3 cell line.•Transferrin-nanoparticles confer protection against amyloid-beta fibrillation.•Great potential for neuroprotection in Alzheimer´s disease. 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 μM) 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. [Display omitted]