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In vitro and in vivo pharmacokinetic study of a dexamethasone-releasing silicone for cochlear implants

  • Otology
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Abstract

Cochlear implants have been widely used for patients with profound hearing loss and partial deafness. Residual low-frequency hearing, however, may deteriorate due to insertion trauma and tissue response around the electrode array. The present study investigated in vitro and in vivo release of dexamethasone from silicone used for cochlear implant electrode carriers. The in vitro experiment involved an apparatus simulating the inner ear fluid environment in humans. Release from two sizes of silicone films (200 µm × 1 mm × 10 mm and 500 µm × 1 mm × 10 mm), each loaded with 2 % dexamethasone, and was measured for 24 weeks. In the in vivo experiment, silicone rods loaded with 2 or 10 % dexamethasone, respectively, were implanted into the scala tympani of guinea pigs. Perilymph concentrations were measured during the first week after implantation. The results showed that dexamethasone was released from the silicone in a sustained manner. After a burst release, perilymph concentration was similar for silicone incorporated with 2 and 10 % dexamethasone, respectively. The similar pharmacokinetic profile was found in the in vitro experiment. The period of sustained drug delivery was maintained for 20 weeks in vitro and for 1 week in vivo. The results of the present study suggest that drugs like dexamethasone are released in a controlled manner from silicon electrode carriers of cochlear implants. Further studies will identify optimal release profiles for the use with cochlear implants to improve their safety and long-term performance.

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Acknowledgments

We thank Dr. Heike Schneider from Institute of Clinical Chemistry and Phatobiochemistry, Klinikum rechts der Isar, for her kind assistance with the HPLC assay. We gratefully acknowledge Michael Todd for medical writing assistance following the preparation of a version of this manuscript. We thank Prof. Karsten Mäder (Halle/Saale) for comments on the manuscript. The authors express their sincere gratitude to the MED-EL Medical Electronics, Innsbruck, Austria for providing financial supports.

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Correspondence to Jan Kiefer.

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The study was supported by a research grant from MED-EL Medical Electronics, Innsbruck, Austria to the Technical University of Munich, Germany. The authors have no conflicts of interest to declare.

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Liu, Y., Jolly, C., Braun, S. et al. In vitro and in vivo pharmacokinetic study of a dexamethasone-releasing silicone for cochlear implants. Eur Arch Otorhinolaryngol 273, 1745–1753 (2016). https://doi.org/10.1007/s00405-015-3760-0

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