Antioxidants derived
from nature, such as ellagic acid (EA), demonstrated
high potency to mitigate neuronal oxidative stress and related pathologies,
including Parkinson’s disease. However, the application of
EA is limited due to its toxicity at moderate doses and poor solubility,
cellular permeability, and bioavailability. Here, we introduce a sustainably
resourced, green nanoencasement strategy to overcome the limitations
of EA and derive synergistic effects to prevent oxidative stress in
neuronal cells. Chitosan, with its high biocompatibility, potential
antioxidant properties, and flexible surface chemistry, was chosen
as the primary component of the nanoencasement in which EA is immobilized.
Using a rotenone model to mimic intracellular oxidative stress, we
examined the effectiveness of EA and chitosan to limit cell death.
Our studies indicate a synergistic effect between EA and chitosan
in mitigating rotenone-induced reactive oxygen species death. Our
analysis suggests that chitosan encapsulation of EA reduces the inherent
cytotoxicity of the polyphenol (a known anticancer molecule). Furthermore,
its encapsulation permits its delivery via a rapid burst phase and
a relatively slow phase making the nanohybrid suitable for drug release
over extended time periods.