Uric Acid Released from Poly (Lactic-co-Glycolic Acid) Nanoparticles Mitigates Glutamate-Induced Excitotoxicity of Spinal Cord Neurons

Spinal cord injury (SCI) is often compounded by secondary damage caused by glutamate-induced excitotoxicity (GIE), where excessive glutamate release results in neuronal damage by overstimulation of glutamate receptors. This process leads to mitochondrial dysfunction, oxidative stress, and neuronal death. Uric acid (UA) has been identified as a potential neuroprotective molecule due to its antioxidant properties, but its limited solubility poses challenges for clinical use. To address this issue, we encapsulated UA in poly (lactic-co-glycolic acid) nanoparticles (UA-NPs) using a modified double emulsion technique to enhance stability and delivery of UA. Spinal cord cultures were subjected to GIE, followed by treatment with UA-NPs or empty nanoparticles. Neuronal survival was assessed with immunocytochemistry for the neuronal marker microtubule-associated protein 2 (MAP2), which revealed that treatment with UA-NPs resulted in significantly higher cell survival compared to cultures treated with empty nanoparticles. These findings suggest that UA-NPs provide neuroprotection to spinal cord neurons in vitro and may serve as a promising localized drug delivery system for SCI treatment, offering a targeted approach to mitigate secondary injury.