Native PEG-PLGA Attenuates β-Amyloid Aggregation and Toxicity under In Vitro Conditions.

Area of Science:

• Neuroscience
• Biomaterials Science
• Pharmacology

Background:

• Amyloid-β (Aβ) peptide self-aggregation is central to Alzheimer's disease (AD) pathogenesis.
• Effective AD treatments are limited by the blood-brain barrier and disease heterogeneity.
• Previous studies showed native poly(lactic-co-glycolic acid) (PLGA) nanoparticles can reduce Aβ aggregation and toxicity.

Purpose of the Study:

• To synthesize and characterize PEGylated native PLGA nanoparticles (PEG-PLGA-1) to reduce reticuloendothelial system (RES) clearance.
• To evaluate the effects of PEG-PLGA-1 on Aβ aggregation and toxicity.
• To assess the therapeutic potential of PEG-PLGA-1 for Alzheimer's disease.

Main Methods:

• Synthesis and characterization of PEGylated native PLGA nanoparticles (PEG-PLGA-1).
• Thioflavin T kinetic assay, dynamic light scattering, and fluorescence imaging to assess Aβ aggregation and disassembly.
• Cell viability assays using mouse primary cortical cultured neurons exposed to Aβ.

Main Results:

• PEG-PLGA-1 nanoparticles demonstrated increased stability and reduced RES clearance.
• PEG-PLGA-1 inhibited Aβ peptide aggregation and promoted the disassembly of existing Aβ aggregates.
• PEG-PLGA-1 were found to be non-toxic and significantly enhanced neuronal viability against Aβ-induced toxicity.

Conclusions:

• Native PEG-PLGA-1 nanoparticles effectively inhibit Aβ aggregation and trigger the disassembly of Aβ aggregates.
• PEG-PLGA-1 nanoparticles protect neurons from Aβ-mediated toxicity.
• These findings highlight the therapeutic potential of PEG-PLGA-1 nanoparticles for Alzheimer's disease treatment.