A novel controlled local drug delivery system for inner ear disease

David P. Paulson, Waleed Abuzeid, Hao Jiang, Tomoyuki Oe, Bert W. O'Malley, Daqing Li

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

PURPOSE: Our goal is to develop a novel drug delivery system that can potentially improve clinical outcomes compared to current methods of dosing drugs such as dexamethasone or gentamicin. This system focuses on a single local application to the inner ear via the round window membrane. HYPOTHESIS: A chitosan-glycerophosphate (CGP)-hydrogel based drug delivery system can be engineered to provide local and sustained drug release to the inner ear. STUDY DESIGN: In vitro: drug release and (CGP)-hydrogel matrix degradation were characterized using dexamethasone as a model drug. In vivo: dexamethasone laden CGP-hydrogel was placed in the round window niche of mice. Perilymph samples were obtained from the oval window and analyzed for dexamethasone. The impact of CGP-hydrogel on auditory function was evaluated. RESULTS: In vitro: A CGP-hydrogel was designed to release 92% of the dexamethasone load over 4 consecutive days with concurrent degradation of the hydrogel matrix. In vivo: After surgical placement of CGP-hydrogel to the round window niche, we detected elevated levels of dexamethasone in perilymph for 5 days. Auditory function testing revealed a temporary hearing loss in the immediate postoperative period, which resolved by the 10th postoperative day. CONCLUSIONS: We report the development of CGP-hydrogel, a biodegradable matrix that achieves local, sustained delivery of dexamethasone to the inner ear. There were no significant complications resulting from the surgical procedure or the administration of CGP-hydrogel to our murine model.

Original languageEnglish (US)
Pages (from-to)706-711
Number of pages6
JournalLaryngoscope
Volume118
Issue number4
DOIs
StatePublished - Apr 2008

Keywords

  • C57
  • Chitosan glycerophosphate
  • Dexamethasone
  • Drug delivery
  • Ear
  • Hydrogel
  • Mouse
  • Perilymph analysis

ASJC Scopus subject areas

  • Otorhinolaryngology

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    Paulson, D. P., Abuzeid, W., Jiang, H., Oe, T., O'Malley, B. W., & Li, D. (2008). A novel controlled local drug delivery system for inner ear disease. Laryngoscope, 118(4), 706-711. https://doi.org/10.1097/MLG.0b013e31815f8e41