A novel controlled local drug delivery system for inner ear disease.
OBJECTIVE
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.


OBJECTIVE
A chitosan-glycerophosphate (CGP)-hydrogel based drug delivery system can be engineered to provide local and sustained drug release to the inner ear.


METHODS
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.
Paulson
David P
DP
Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Abuzeid
Waleed
W
Jiang
Hao
H
Oe
Tomoyuki
T
O'Malley
Bert W
BW
Li
Daqing
D
D020341:Absorbable Implants; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001309:Auditory Threshold / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005994:Glycerophosphates / Q000737:chemistry; D006309:Hearing / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007759:Labyrinth Diseases / Q000188:drug therapy*; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D023421:Models, Animal; D010046:Oval Window, Ear / Q000378:metabolism; D010498:Perilymph / Q000737:chemistry; D012405:Round Window, Ear / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D005994:Glycerophosphates; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D003907:Dexamethasone; D048271:Chitosan