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

Abstract

Inflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer’s disease (AD), growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of anti-inflammatory molecules to macrophages stimulated via direct incubation with amyloid-β fibers. 200 nm spherical polymeric nanoconstructs (SPNs) and 1,000 nm discoidal polymeric nanoconstructs (DPNs) were synthesized using poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and lipid chains as building blocks. First, the internalization propensity in macrophages of both nanoparticles was assessed via cytofluorimetric and confocal microscopy analyses, demonstrating that SPNs are by far more rapidly taken up as compared to DPNs (99.6 ± 0.11 vs 14.4 ± 0.06%, within 24 h). Then, Curcumin-loaded SPNs (Curc-SPNs) were realized by encapsulating Curcumin, a natural anti-inflammatory molecule, within the PLGA core of SPNs. Finally, Curc-SPNs were shown to diminish up to 6.5-fold the production of pro-inflammatory cytokines—IL-1β; IL-6, and TNF-α—in macrophages stimulated via amyloid-β fibers. Although more sophisticated in vitro models and systematic analyses on the blood–brain barrier permeability are critically needed, these findings hold potential in the development of nanoparticles for modulating inflammation in AD.

miR-103 Promotes Neurite Outgrowth and Suppresses Cells Apoptosis by Targeting Prostaglandin-Endoperoxide Synthase 2 in Cellular Models of Alzheimer’s Disease

“…However, no published report has explored the effect of Aβ1–42 on miR-103, while inversely, miR-103 is observed to directly target ADAM 10, and ADAM 10 is a critical gene in modulating the formation of Aβ1–42 (Jiao et al, 2017 ). The possible explanation of this result might be that Aβ1–42 promoted neuronal inflammation, which reduced the expression of miR-103 (Ameruoso et al, 2017 ; Fang et al, 2018 ; Zhang et al, 2018 ), nevertheless, this inference needed to be validated in further studies. Subsequently, miR-103 mimic and inhibitor plasmids were used for transfection instead of lentivirus due to the late effect initiation of lentivirus in cells (Shearer and Saunders, 2015 ).…”

Highly Bioavailable Forms of Curcumin and Promising Avenues for Curcumin-Based Research and Application: A Review

“…With the development of curcumin formulations with very high bioavailability, it should now be possible to exploit these activities in Alzheimer's disease, multiple sclerosis, Parkinson's disease and amyotrophic lateral sclerosis (ALS) [38][39][40][41][42]. For example, curcumin formulations that were found to prevent accumulation of amyloid beta protein plaque and neurofibrillary tangles in animal models of Alzheimer's disease are exceedingly promising [60,61]. Other neurological disorders that can benefit from highly bioavailable curcumin formulations include traumatic brain injury (TBI) [62] and neuropsychiatric disorders as post-traumatic stress disorder (PTSD), depressive disorders, psychotic disorders, bipolar disorder, obsessive-compulsive disorder (OCD) and autism [63].…”

Therapeutic Potential and Recent Advances of Curcumin in the Treatment of Aging-Associated Diseases

“…Curcumin-loaded spherical polymeric nanoconstructs with lipid chains was assessed in vitro using RAW 264.7 cells. The nanoconstructs significantly modulated the production of pro-inflammatory cytokines without any cytotoxic effect [ 66 ]. Curcumin-conjugated magnetic nanoparticles bind with amyloid plaques in mouse brains, which was confirmed through immunohistochemical studies and magnetic resonance images.…”