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A Polymer-Based Extended Release System for Stable, Long-term Intracochlear Drug Delivery

Pierstorff, Erik*; Chen, Shanshan; Chaparro, Maria Paola; Cortez, John M. Jr.; Chen, Yen-Jung; Ryu, Su Young§; Tsai, Sherry M.§; Baum, Marc M.§; Yang, Wan Wan*; Kalinec, Federico||; Smith, Thomas*; Ludwig, Stacey; Slattery, William H.*

doi: 10.1097/MAO.0000000000001977
BASIC SCIENCE
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Objective: Investigate a new polymer-based drug coating suitability for safe intracochlear delivery and ability to maintain long-term physiologically active levels of the corticosteroid fluticasone propionate.

Study Design: In vitro dissolution study to evaluate release profiles of polymer-coated drug particles and in vivo studies using a guinea pig model to measure perilymph drug concentrations at specific time points after implantation with polymer-coated drug particles and evaluate their effect on hearing function.

Methods: Polymer-coated fluticasone propionate (FP) particles were surgically implanted in guinea pigs through the round window membrane into the cochlear scala tympani. In the pilot study, pre- and post-op hearing thresholds were conducted on days 7, 14, and 42. In a second study, post-op hearing thresholds were conducted on days 90, 120, and 180. Perilymph drug concentrations were measured on the same time points.

Results: In 15 of 16 animals from day 7 through day 90, drug levels were within the targeted range, with no initial burst release detected. Drug was present in all animals on day 90 and was detected in some animals at 120 and 180 days. Hearing was tested and compared with non-implanted ears. Very good hearing preservation was observed in ears implanted with intracochlear particles when compared with contralateral ears.

Conclusions: The polymer-based extended release system is effective in providing long-term, stable drug delivery for at least 90 days with good hearing outcomes. The results of this study support the potential for achieving long-term drug delivery with a single intracochlear administration.

*O-Ray Pharma, Inc.

Auritec Pharmaceuticals, Inc., Pasadena

House Research Institute, House Ear Clinic

§Oak Crest Institute of Science, Monrovia

||Department of Head and Neck Surgery, David Geffen School of Medicine at the University of California, Los Angeles, California

Address correspondence and reprint requests to Erik Pierstorff, Ph.D., O-Ray Pharma, 2285 E. Foothill Blvd, Pasadena, CA 91107; E-mail: epierstorff@oraypharma.com

Guinea pig studies were performed at House Research Institute. All other studies and analyses were conducted at the facilities of O-Ray Pharma and Oak Crest Institute of Science.

Source of financial support or funding: Studies were supported by O-Ray Pharma and NIH R44DC008477.

Disclosure: Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under Award Number R44DC008477. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

E.P., T.S., and W.S. own stock in O-Ray Pharma.

Copyright © 2018 by Otology & Neurotology, Inc. Image copyright © 2010 Wolters Kluwer Health/Anatomical Chart Company