Zein nanoparticles loaded with chloroquine improve functional recovery and attenuate neuroinflammation after spinal cord injury.

• Zein nanoparticles for sustained-release chloroquine were successfully prepared. • Zein nanoparticles reduced chloroquine toxicity through sustained release. • Chloroquine released from zein nanoparticles inhibited neuroinflammation. • Degradation products of zein nanoparticles promoted M2 microglia polarization. Inflammation is a pivotal molecular event in secondary spinal cord injury (SCI). However, chloroquine (CQ) is an anti-malarial drug with remarkable anti-inflammatory effects. Zein is a biodegradable biomaterial derived from natural-plant protein and is widely applied in drug sustained-release carriers due to its promising biocompatibility and biodegradability. In this research, we investigated the significant effects and underlying molecular mechanisms of zein nanoparticles (NPs) loaded with CQ in SCI. More importantly, we found that local delivery of Zein-CQ NPs after SCI could significantly improved functional recovery, inhibited neuronal apoptosis, alleviated neuroinflammation and enhanced M2 phenotype microglia polarization. Mechanistically, our findings further demonstrated that local administration of Zein-CQ NPs inhibited activation of the MAPK/NF-κB signaling pathway after SCI in rats. Moreover, Zein-CQ NPs reduced the release of pro-inflammatory factors and augmented the protein expression of M2 phenotype microglia in lipopolysaccharide (LPS)-stimulated BV2 cells. Our findings imply that local delivery of Zein-CQ NPs produces promising therapeutic benefits for the treatment and management of SCI. [ABSTRACT FROM AUTHOR]