Nanoformulated metformin enhanced the treatment of spinal cord injury

Spinal cord injury (SCI) leads to immediate disruption of neuronal membranes neuronal death, and inflammation, which in turn trigger secondary injury. Few therapies against SCI have been developed. Metformin displays anti-inflammatory, anti-oxidant, anti-apoptotic, and neuroprotective capacity and may therefore alleviate SCI. However, it shows a short half-life, poor water solubility, fast absorption, rapid clearance, and a lack of targeted delivery options. Here we attempt to overcome these obstacles by developing zein-based spherical nanoparticles containing the peptide CAQK for targeted delivery of metformin (CAQK-MET-NPs) in SCI. We investigated the pharamocodynamics and effects of CAQK-MET-NPs on neural recovery in cell models as well as a rat SCI model using histopathology, immunohistochemistry, behavioral tests, and various imaging techniques. CAQK-MET-NPs exerted strong anti-inflammatory and neuroprotective activities in vitro and in vivo, promoting the spinal cord repair and partial recovery of motor function after SCI. This study thus provides an important foundational step towards potential SCI therapy.