Novel therapy for hearing loss: delivery of insulin-like growth factor 1 to the cochlea using gelatin hydrogel

Otol Neurotol. 2007 Oct;28(7):976-81. doi: 10.1097/MAO.0b013e31811f40db.

Abstract

Hypothesis: Local application of recombinant human insulin-like growth factor 1 (rhIGF-1) via a biodegradable hydrogel after onset of noise-induced hearing loss (NIHL) can attenuate functional and histologic damage.

Background: The biodegradable gelatin hydrogel makes a complex with drugs by static electric charges and releases drugs by degradation of gelatin polymers. We previously demonstrated the efficacy of local rhIGF-1 application via hydrogels before noise exposure for prevention of NIHL.

Methods: First, we used an enzyme-linked immunosorbent assay to measure human IGF-1 concentrations in the cochlear fluid after placing a hydrogel containing rhIGF-1 onto the round window membrane of guinea pigs. Second, the functionality and the histology of guinea pig cochleae treated with local rhIGF-1 application at different concentrations after noise exposure were examined. Control animals were treated with a hydrogel immersed in physiologic saline alone.

Results: The results revealed sustained delivery of rhIGF-1 into the cochlear fluid via the hydrogel. The measurement of auditory brainstem responses demonstrated that local rhIGF-1 treatment significantly reduced the threshold elevation from noise. Histologic analysis exhibited increased survival of outer hair cells by local rhIGF-1 application through the hydrogel.

Conclusion: These findings indicate that local rhIGF-1 treatment via gelatin hydrogels is effective for treatment of NIHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Auditory Threshold / physiology
  • Chemistry, Pharmaceutical
  • Cochlea*
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Female
  • Gelatin
  • Guinea Pigs
  • Hearing Loss, Noise-Induced / drug therapy*
  • Hearing Loss, Noise-Induced / pathology
  • Hydrogels
  • Immunohistochemistry
  • Injections
  • Insulin-Like Growth Factor I / administration & dosage*
  • Insulin-Like Growth Factor I / adverse effects
  • Insulin-Like Growth Factor I / therapeutic use*
  • Noise / adverse effects
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use

Substances

  • Hydrogels
  • Recombinant Proteins
  • Insulin-Like Growth Factor I
  • Gelatin