Redox-Responsive Curcumin-Loaded Polymeric Nanoparticles for Targeted Therapy of Parkinson’s Disease-Associated Neuroinflammation

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, oxidative stress, and chronic neuroinflammation. The present study focuses on the development of redox-responsive curcumin-loaded polymeric nanoparticles as a targeted therapeutic strategy for PD-associated neuroinflammation. Curcumin was encapsulated within biodegradable PLGA/PEG-based nanoparticles incorporating disulfide linkages to enable reactive oxygen species (ROS)-triggered drug release. The formulated nanoparticles were evaluated for physicochemical properties, in vitro drug release behavior, cellular uptake, cytotoxicity, anti-inflammatory activity, oxidative stress modulation, and in vivo neuroprotective efficacy. The nanoparticles exhibited uniform nanoscale size distribution, high encapsulation efficiency, and stable surface charge, indicating suitability for brain-targeted delivery. In vitro studies demonstrated controlled drug release under physiological conditions and significantly enhanced release under oxidative environments, confirming redox responsiveness. Cellular studies in microglial and neuronal models showed improved uptake, minimal cytotoxicity, and significant reduction in ROS levels and apoptosis. Anti-inflammatory assays revealed suppression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and inhibition of microglial activation. Furthermore, oxidative stress markers were significantly reduced with a concomitant increase in antioxidant enzyme activity (SOD, CAT, and GSH). In vivo results in toxin-induced PD models demonstrated improved motor coordination, enhanced neuronal survival, and reduced neuroinflammation. Overall, the developed nanocarrier system effectively enhances curcumin bioavailability and therapeutic efficacy, offering a promising multifunctional approach for the management of Parkinson’s disease.