Drug delivery system of hepatocyte growth factor for the treatment of vocal fold scarring in a canine model.
OBJECTIVE
Vocal fold scarring remains a therapeutic challenge. Previous studies have indicated that hepatocyte growth factor (HGF), a strong antifibrotic element, has therapeutic potential for restoring scarred vocal folds. To enhance the effect of HGF in vivo, we developed a novel drug delivery system (DDS) in which HGF is embedded in gelatin hydrogel and continuously released over a period of 2 weeks. In the present study we investigated the therapeutic efficacy of the HGF DDS on vocal fold scarring by using a canine model.


METHODS
The vocal folds of 8 beagles were unilaterally scarred by stripping the entire layer of the lamina propria. The contralateral vocal folds were kept intact as normal controls. One month after the procedure, hydrogels (0.5 mL) containing 1 microg of HGF were injected into the scarred vocal folds of 4 dogs (HGF-treated group), whereas hydrogels containing saline solution were injected in the other 4 dogs (sham group). Histologic and vibratory examinations were completed for each group 6 months after the initial surgery.


RESULTS
The excised larynx experiments showed significantly better vibration in terms of mucosal wave amplitude and glottal closure in the HGF-treated group compared to the sham group. Histologic evaluation of the vocal folds indicated remarkable reduction in collagen deposition and tissue contraction, with favorable restoration of hyaluronic acid and elastin in the HGF-treated group.


CONCLUSIONS
The present findings suggest that the novel HGF DDS may provide favorable effects in restoring the vibratory properties of scarred vocal folds.
Ohno
Tsunehisa
T
Dept of Otolaryngology-Head and Neck Surgery, Kyoto University Graduate School of Medicine, 54, Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Hirano
Shigeru
S
Kanemaru
Shin-ichi
S
Yamashita
Masaru
M
Umeda
Hiroo
H
Suehiro
Atsushi
A
Tamura
Yoshihiro
Y
Nakamura
Tatsuo
T
Ito
Juichi
J
Tabata
Yasuhiko
Y
D000818:Animals; D002921:Cicatrix / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D016503:Drug Delivery Systems / Q000295:instrumentation*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D016896:Treatment Outcome; D014827:Vocal Cords / Q000473:pathology*
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D017228:Hepatocyte Growth Factor