Evaluation of the neuroprotective effects of alpha lipoic acid-loaded folate-conjugated chitosan nanoparticles against 6-OHDA-induced apoptosis and oxidative stress in an in vitro Parkinson’s disease model

Abstract Folate receptors, which mediate the cellular uptake of folic acid (FA) for essential processes such as DNA synthesis and repair, are expressed on neurons affected in Parkinson’s disease (PD). While the etiology of PD remains incompletely understood, oxidative stress is implicated as a key contributor. Alpha-lipoic acid (ALA) is a potent antioxidant; however, its therapeutic application is limited by instability, low bioavailability, and an unpleasant odor. Nanotechnology offers a promising strategy to overcome these limitations. This study aimed to develop and characterize folic acid-conjugated chitosan nanoparticles encapsulating ALA (FA-CS-ALA NPs) and to evaluate their efficacy against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. The FA-CS-ALA NPs, characterized by transmission electron microscopy, exhibited an irregular spherical morphology. Dynamic light scattering (DLS) analysis determined an average particle size of 658.13 nm and a polydispersity index (PDI) of 0.17, indicating moderate size distribution. In vitro studies using SH-SY5Y neuroblastoma cells demonstrated that 6-OHDA exposure significantly increased oxidative stress, neuroinflammation, and apoptosis. Both free ALA and FA-CS-ALA NPs effectively mitigated these deleterious effects. Notably, the FA-CS-ALA NPs exhibited superior neuroprotective efficacy compared to free ALA, suggesting that the folate-conjugated nanocarrier enhances therapeutic delivery.