Zein-Based Triple-Drug Nanoparticles to Promote Anti-inflammatory Responses for Nerve Regeneration after Spinal Cord Injury.

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem was developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor were combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles were internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibited the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protected SH-SY5Y cells from the toxicity of H2 O2 . In a rat model of spinal cord injury, the nanoparticles mitigated inflammation and promoted spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles functioned better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple-drug nanoparticles show promise for treating spinal cord injury. This article is protected by copyright. All rights reserved.