Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

Int J Pharm. 2013 Oct 15;455(1-2):148-58. doi: 10.1016/j.ijpharm.2013.07.045. Epub 2013 Jul 31.

Abstract

We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low βIII tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals.

Keywords: Alginate; GDNF; Injectable hydrogel; Microspheres; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry*
  • Animals
  • Disease Models, Animal
  • Female
  • Gait / drug effects
  • Glial Cell Line-Derived Neurotrophic Factor / administration & dosage*
  • Glial Cell Line-Derived Neurotrophic Factor / chemistry
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Injections
  • Lactic Acid / chemistry
  • Microspheres
  • Neurites / drug effects
  • Neurites / physiology
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Long-Evans
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / physiopathology

Substances

  • Alginates
  • Glial Cell Line-Derived Neurotrophic Factor
  • Hexuronic Acids
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Polyglycolic Acid
  • Lactic Acid
  • Glucuronic Acid