Partially funded by NIH Training Grant 5T32 DC005363-04.
A Novel Controlled Local Drug Delivery System for Inner Ear Disease†
Article first published online: 2 JAN 2009
Copyright © 2008 The Triological Society
Volume 118, Issue 4, pages 706–711, April 2008
How to Cite
Paulson, D. P., Abuzeid, W., Jiang, H., Oe, T., O'Malley, B. W. and Li, D. (2008), A Novel Controlled Local Drug Delivery System for Inner Ear Disease. The Laryngoscope, 118: 706–711. doi: 10.1097/MLG.0b013e31815f8e41
- Issue published online: 2 JAN 2009
- Article first published online: 2 JAN 2009
- Manuscript Accepted: 24 OCT 2007
- Drug delivery;
- chitosan glycerophosphate;
- perilymph analysis
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.