Targeted-delivery of nanomedicine-enabled methylprednisolone to injured spinal cord promotes neuroprotection and functional recovery after acute spinal cord injury in rats

To date, no therapy has been proven to be efficacious in fully restoring neurological functions after spinal cord injury (SCI). Systemic high-dose methylprednisolone (MP) improves neurological recovery after acute SCI in both animal and human. MP therapy remains controversial due to its modest effect on functional recovery and significant adverse effects. To overcome the limitation of MP therapy, we have developed a N-(2-hydroxypropyl) methacrylamide copolymer-based MP prodrug nanomedicine (Nano-MP) that can selectively deliver MP to the SCI lesion when administered systemically in a rat model of acute SCI. Our in vivo data reveal that Nano-MP is significantly more effective than free MP in attenuating secondary injuries and neuronal apoptosis. Nano-MP is superior to free MP in improving functional recovery after acute SCI in rats. These data support Nano-MP as a promising neurotherapeutic candidate, which may provide potent neuroprotection and accelerate functional recovery with improved safety for patients with acute SCI. Novel N-(2-hydroxypropyl) methacrylamide copolymer-based methylprednisolone (MP) prodrug nanomedicine (Nano-MP) were successfully developed. The intravenous Nano-MP administration is able to selectively deliver MP to the inflamed spinal cord injury site with improved capacities to inhibit inflammation and lipid peroxidation, thereby promoting neuroprotection and functional recovery in a rat model of acute spinal cord injury (SCI). These extraordinary findings and the significantly improved safety profile presented in the companion paper in this issue of the journal strongly support the potential of Nano-MP for continued efforts toward clinical translation as a highly promising drug candidate for improved clinical management of SCI and its complications. [Display omitted]