Sustained delivery of chondroitinase ABC by poly(propylene carbonate)-chitosan micron fibers promotes axon regeneration and functional recovery after spinal cord hemisection

Brain Res. 2015 Oct 22:1624:469-478. doi: 10.1016/j.brainres.2015.08.018. Epub 2015 Aug 24.

Abstract

We describe the sustained delivery of chondroitinase ABC (ChABC) in the hemisected spinal cord using polypropylene carbonate (PPC) electrospun fibers with chitosan (CS) microspheres as a vehicle. PPC and ChABC-loaded CS microspheres were mixed with acetonitrile, and micron fibers were generated by electrospinning. ChABC release was assessed in vitro with high-performance liquid chromatography (HPLC) and revealed stabilized and prolonged release. Moreover, the released ChABC showed sustained activity. PPC-CS micron fibers with or without ChABC were then implanted into a hemisected thoracic spinal cord. In the following 4 weeks, we examined functional recovery and performed immunohistochemical analyses. We found that sustained delivery of ChABC promoted axon sprouting and functional recovery and reduced glial scarring; PPC-CS micron fibers without ChABC did not show these effects. The present findings suggest that PPC-CS micron fibers containing ChABC are a feasible option for spinal cord injury treatment. Furthermore, the system described here may be useful for local delivery of other therapeutic agents.

Keywords: ChABC; Chitosan; Electrospinning; PPC; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / drug effects*
  • Chitosan / therapeutic use
  • Chondroitin ABC Lyase / therapeutic use*
  • Disease Models, Animal
  • Exploratory Behavior / drug effects
  • Female
  • Gene Expression Regulation / drug effects
  • Motor Activity / drug effects
  • Nerve Tissue Proteins / metabolism
  • Propane / analogs & derivatives
  • Propane / therapeutic use
  • Rats
  • Rats, Wistar
  • Recovery of Function / drug effects*
  • Regeneration / drug effects*
  • Spinal Cord Injuries / drug therapy*
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Nerve Tissue Proteins
  • propylene carbonate
  • Chitosan
  • Chondroitin ABC Lyase
  • Propane