Quercetin lipid nanoparticles functionalized with transferrin for Alzheimer's disease

Area of Science:

• Neuroscience
• Nanotechnology
• Pharmacology

Background:

• Alzheimer's disease is a neurodegenerative disorder characterized by amyloid-beta aggregation.
• Quercetin exhibits neuroprotective properties but faces challenges in crossing the blood-brain barrier.
• Lipid nanoparticles offer a promising delivery system for therapeutic agents to the brain.

Purpose of the Study:

• To encapsulate quercetin into solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC).
• To functionalize these nanoparticles with transferrin for enhanced blood-brain barrier (BBB) penetration.
• To evaluate the potential of these nanoparticles in inhibiting amyloid-beta aggregation for Alzheimer's disease therapy.

Main Methods:

• Quercetin was encapsulated in SLN and NLC, followed by transferrin functionalization.
• Nanoparticle characterization included Nuclear Magnetic Resonance (NMR), Fourier-Transform Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), size, and zeta potential measurements.
• Cytotoxicity was assessed using Lactate Dehydrogenase (LDH) assays on hCMEC/D3 cells.
• Permeability studies across hCMEC/D3 cell monolayers and amyloid-beta fibril formation inhibition assays were performed.

Main Results:

• Transferrin functionalization was confirmed by NMR and FTIR.
• Spherical nanoparticles around 200 nm with zeta potential > -30 mV were obtained.
• High quercetin entrapment efficiency (80-90%) was achieved.
• Nanoparticles showed no cytotoxicity at 30 μM concentration after 4h incubation.
• NLC demonstrated higher permeability across the BBB model.
• NLC-transferrin inhibited amyloid-beta aggregation.

Conclusions:

• Transferrin-functionalized SLN and NLC are suitable for brain delivery of quercetin.
• NLC-transferrin nanoparticles show significant potential for Alzheimer's disease treatment by inhibiting amyloid-beta aggregation and facilitating BBB passage.