Galantamine-loaded PLGA nanoparticles reduce oxidative stress and inflammation in a rat model of spinal cord injury

Spinal cord injury (SCI) represents a debilitating condition with no effective treatments currently available. Previous research demonstrated that galantamine improves functional outcomes in SCI models. However, systemic administration results in limited target tissue bioavailability. This study aimed to develop and evaluate the therapeutic potential of galantamine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles for SCI treatment. Galantamine-containing PLGA particles (PG) were synthesized via electrospraying, yielding nanoparticles with 568 nm average diameter, - 23 mV zeta potential, 12.87% encapsulation efficiency, and drug release over 35 days. In a rat contusion SCI model, animals received direct implantation of galantamine alone, empty PLGA particles, or PG. Locomotor assessment over 6 weeks revealed significant functional improvements only in the PG group. Tissue analysis at 3 days and 6 weeks post-injury showed that PG treatment significantly reduced oxidative stress markers as ROS production and lipid peroxidation, and selectively reduced IL-1β but did not significantly affect IL-6 levels. Flow cytometry analysis revealed reduced GFAP expression in PLGA and PG-treated groups, indicating decreased astrocyte activation, while neuronal markers (neurofilament-M, βIII-tubulin) and oligodendrocyte markers (O4) showed no significant changes between groups. These results demonstrate that galantamine-loaded PLGA nanoparticles provide superior therapeutic outcomes through targeted anti-inflammatory, antioxidant, and glial modulation mechanisms.