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