A Novel Controlled Local Drug Delivery System for Inner Ear Disease

Authors

  • David P. Paulson MD,

    1. Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania, U.S.A.
    Search for more papers by this author
  • Waleed Abuzeid MD,

    1. Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania, U.S.A.
    Search for more papers by this author
  • Hao Jiang PhD,

    1. Department of Pharmacology, University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania, U.S.A.
    Search for more papers by this author
  • Tomoyuki Oe PhD,

    1. Department of Pharmacology, University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania, U.S.A.
    Search for more papers by this author
  • Bert W. O'Malley MD,

    1. Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania, U.S.A.
    Search for more papers by this author
  • Daqing Li MD

    Corresponding author
    1. Department of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania, U.S.A.
    • Daqing Li, MD, University of Pennsylvania School of Medicine, Department of Otorhinolaryngology, 421 Curie Blvd, BRB 11/111 Room 1149, Philadelphia, PA 19104, U.S.A.
    Search for more papers by this author

  • Partially funded by NIH Training Grant 5T32 DC005363-04.

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.

Ancillary