METALLIC NANOPARTICLES AS CARRIERS OF NEUROPROTECTIVE AGENTS FOR THE CENTRAL NERVOUS SYSTEM

Stroke remains one of the leading causes of mortality and long-term disability worldwide, frequently resulting in irreversible brain injury and functional impairment. Although major advances have been achieved in the understanding of ischemic mechanisms and in acute clinical management, effective neuroprotective strategies for the central nervous system (CNS) are still limited. A major obstacle to pharmacological intervention is the restricted delivery of therapeutic agents to the brain, primarily imposed by the blood–brain barrier (BBB). In this context, metallic nanoparticles, particularly gold nanoparticles (AuNPs), represent a promising platform for the targeted delivery of neuroprotective compounds to ischemic neural tissue. This study proposes the use of functionalized AuNPs as carriers of neuroprotective agents aiming to enhance drug biodistribution, increase therapeutic specificity, and reduce systemic side effects. AuNPs were synthesized by the citrate reduction method and subsequently functionalized with different neuroprotective drugs. The physicochemical properties of the nanoparticles were assessed by UV–vis spectroscopy, transmission electron microscopy, and zeta potential analysis. Neuroblastoma cell cultures were used to evaluate cytotoxicity, while brain tissue slices were employed to assess the neuroprotective efficacy of conjugated AuNPs. Cell viability assays, including MTT and LDH, and apoptosis-related assays involving caspase-3, caspase-8, and caspase-9 were performed under oxidative stress conditions. In vitro BBB models were further used to investigate the ability of functionalized AuNPs to cross this biological barrier. The results indicate that drug-functionalized AuNPs preserved suitable physicochemical characteristics after conjugation, including adequate hydrodynamic diameter and stable surface charge. Conjugated AuNPs showed low cytotoxicity and substantial protection against oxidative stress-induced neuronal apoptosis. Moreover, permeability assays demonstrated that functionalized AuNPs crossed the BBB model more efficiently than free drugs, suggesting improved brain delivery. The combined antioxidant properties of AuNPs and the controlled release of neuroprotective agents may provide a synergistic mechanism of action, with potential relevance not only for ischemic stroke but also for neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Overall, functionalized gold nanoparticles constitute an innovative and effective approach for CNS drug delivery. These findings support the potential of AuNP-based nanocarriers to improve neuroprotective therapy by enhancing brain targeting, protecting neurons from oxidative injury, and overcoming BBB-related pharmacological limitations.