Zonisamide-loaded triblock copolymer nanomicelles as a novel drug delivery system for the treatment of acute spinal cord injury

Int J Nanomedicine. 2017 Mar 29:12:2443-2456. doi: 10.2147/IJN.S128705. eCollection 2017.

Abstract

Spinal cord injury (SCI) commonly leads to lifelong disability due to the limited regenerative capacity of the adult central nervous system. Nanomicelles can be used as therapeutic systems to provide effective treatments for SCI. In this study, a novel triblock monomethyl poly(ethylene glycol)-poly(l-lactide)-poly(trimethylene carbonate) copolymer was successfully synthesized. Next, polymeric nanomicelles loaded with zonisamide (ZNS), a Food and Drug Administration-approved antiepileptic drug, were prepared and characterized. The ZNS-loaded micelles (ZNS-M) were further utilized for the treatment of SCI in vitro and in vivo. The obtained ZNS-M were ~50 nm in diameter with good solubility and dispersibility. Additionally, these controlled-release micelles showed significant antioxidative and neuron-protective effects in vitro. Finally, our results indicated that ZNS-M treatment could promote motor function recovery and could increase neuron and axon density in a hemisection SCI model. In summary, these results may provide an experimental basis for the use of ZNS-M as a clinically applicable therapeutic drug for the treatment of SCI in the future.

Keywords: nanomicelles; spinal cord injury; zonisamide.

MeSH terms

  • Acute Disease
  • Animals
  • Antioxidants / pharmacology
  • Axons / drug effects
  • Axons / pathology
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / pathology
  • Cell Death / drug effects
  • Chromatography, Gel
  • Dioxanes / chemical synthesis
  • Dioxanes / chemistry
  • Drug Carriers
  • Drug Delivery Systems*
  • Drug Liberation
  • Isoxazoles / therapeutic use*
  • Magnetic Resonance Imaging
  • Mice
  • Micelles*
  • Nanoparticles / chemistry*
  • Polyesters / chemical synthesis
  • Polyesters / chemistry
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry*
  • Proton Magnetic Resonance Spectroscopy
  • Rats, Sprague-Dawley
  • Spectroscopy, Fourier Transform Infrared
  • Spinal Cord Injuries / drug therapy*
  • X-Ray Diffraction
  • Zonisamide

Substances

  • Antioxidants
  • Dioxanes
  • Drug Carriers
  • Isoxazoles
  • Micelles
  • Polyesters
  • Polymers
  • Polyethylene Glycols
  • trimethylene carbonate
  • Zonisamide
  • poly(lactide)
  • monomethoxypolyethylene glycol