Sodium alginate and naloxone loaded macrophage-derived nanovesicles for the treatment of spinal cord injury

Abstract

Spinal cord injury (SCI) causes Ca2+ overload, which can lead to inflammation and neuronal apoptosis. In this study, we prepared a nanovesicle derived from macrophage membrane (MVs), which encapsulated sodium alginate (SA) and naloxone (NAL) to inhibit inflammation and protect neurons by reducing the free Ca2+concentration at the SCI site. Based on the transmission electron microscopy (TEM) image, the encapsulated sample (NAL–SA–MVs) had a particle size of approximately 134 ± 11 nm and exhibited a sustained release effect. The encapsulation rate of NAL and SA was 82.07% ± 3.27% and 72.13% ± 2.61% in NAL–SA–MVs, respectively. Targeting tests showed that the NAL–SA–MVs could accumulate in large quantities and enhance the concentration of SA and NAL at the lesion sites. In vivo and in vitro studies indicated that the NAL–SA–MVs could decrease the concentration of free Ca2+, which should further alleviate the inflammatory response and neuronal apoptosis. Anti-inflammation results demonstrated that the NAL–SA–MVs could reduce the pro-inflammation factors (iNOS, TNF-α, IL-1β, IL-6) and increase the expression of anti-inflammation factors (IL-10) at the cell and animal level. Concurrently, fluorescence, flow cytometry and western blot characterization showed that the apoptotic condition of the neurons was significantly inhibited. In addition, the motor function of C57 mice were significantly improved after NAL–SA–MVs treatment. In conclusion, it is suggested that the NAL–SA–MVs has tremendous potential in the treatment of SCI.

Keywords

• Naloxone
• Sodium alginate
• Spinal cord injury
• Macrophage membrane
• Inflammation
• Neuroprotection