Effective improvement of the neuroprotective activity after spinal cord injury by synergistic effect of glucocorticoid with biodegradable amphipathic nanomicelles

Abstract

Dexamethasone acetate (DA) produces neuroprotective effects by inhibiting lipid peroxidation and inflammation by reducing cytokine release and expression. However, its clinical application is limited by its hydrophobicity, low biocompatibility and numerous side effects when using large dosage. Therefore, improving DA’s water solubility, biocompatibility and reducing its side effects are important goals that will improve its clinical utility. The objective of this study is to use a biodegradable polymer as the delivery vehicle for DA to achieve the synergism between inhibiting lipid peroxidation and inflammation effects of the hydrophobic-loaded drugs and the amphipathic delivery vehicle. We successfully prepared DA-loaded polymeric micelles (DA/MPEG-PCL micelles) with monodispersed and approximately 25 nm in diameter, and released DA over an extended period in vitro. Additionally, in the hemisection spinal cord injury (SCI) model, DA micelles were more effective in promoting hindlimb functional recover, reducing glial scar and cyst formation in injured site, decreasing neuron lose and promoting axon regeneration. Therefore, our data suggest that DA/MPEG-PCL micelles have the potential to be applied clinically in SCI therapy.