Ameliorating Amyloid-β Fibrils Triggered Inflammation via Curcumin-Loaded Polymeric Nanoconstructs

Area of Science:

• Biomedical Engineering
• Neuroscience
• Nanotechnology

Background:

• Inflammation is implicated in various diseases, including Alzheimer's disease (AD), where it correlates with neuronal damage.
• Microglia, the brain's myeloid cells, play a key role in AD-associated neuroinflammation.
• Targeted delivery of anti-inflammatory agents to macrophages is a potential therapeutic strategy for AD.

Purpose of the Study:

• To engineer and characterize polymeric nanoparticles for delivering anti-inflammatory molecules to macrophages.
• To evaluate the uptake of nanoparticles by macrophages stimulated with amyloid-beta (Aβ) fibers.
• To assess the efficacy of curcumin-loaded nanoparticles in reducing pro-inflammatory cytokine production.

Main Methods:

• Synthesis of spherical polymeric nanoconstructs (SPNs) and discoidal polymeric nanoconstructs (DPNs) using PLGA, PEG, and lipids.
• Assessment of nanoparticle internalization in macrophages via flow cytometry and confocal microscopy.
• Encapsulation of curcumin into SPNs (Curc-SPNs) and evaluation of their effect on cytokine production (IL-1β, IL-6, TNF-α) in Aβ-stimulated macrophages.

Main Results:

• SPNs demonstrated significantly higher uptake in macrophages (99.6%) compared to DPNs (14.4%) within 24 hours.
• Curcumin-loaded SPNs (Curc-SPNs) effectively reduced the production of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α by up to 6.5-fold.
• The engineered nanoparticles successfully delivered an anti-inflammatory payload to activated macrophages.

Conclusions:

• Engineered SPNs are efficiently internalized by macrophages and can deliver anti-inflammatory payloads.
• Curc-SPNs show potential for modulating inflammation in the context of Alzheimer's disease.
• Further in vitro and in vivo studies are needed to validate blood-brain barrier permeability and therapeutic efficacy.