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


CONCLUSIONS
These findings indicate that local rhIGF-1 treatment via gelatin hydrogels is effective for treatment of NIHL.
Lee
Kyu Yup
KY
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nakagawa
Takayuki
T
Okano
Takayuki
T
Hori
Ryusuke
R
Ono
Kazuya
K
Tabata
Yasuhiko
Y
Lee
Sang Heun
SH
Ito
Juichi
J
D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D002626:Chemistry, Pharmaceutical; D003051:Cochlea; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D005780:Gelatin; D006168:Guinea Pigs; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000473:pathology; D020100:Hydrogels; D007150:Immunohistochemistry; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D009622:Noise / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D020100:Hydrogels; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D005780:Gelatin