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Pharmaceutics
Volume 15
Issue 3
10.3390/pharmaceutics15030726
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Article

Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs

by
Wiebke Behrends
1,2,
Katharina Wulf
3,
Stefan Raggl
4,
Max Fröhlich
1,5,
Thomas Eickner
3,
Dana Dohr
6,
Karl-Heinz Esser
2,
Thomas Lenarz
1,7,
Verena Scheper
1,7 and
Gerrit Paasche
1,7,*
1
Department of Otolaryngology, Hannover Medical School, 30625 Hannover, Germany
2
Auditory Neuroethology and Neurobiology, Institute of Zoology, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany
3
Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany
4
MED-EL Medical Electronics, 6020 Innsbruck, Austria
5
MED-EL Research Center, 30625 Hannover, Germany
6
Department of Otorhinolaryngology, Head and Neck Surgery “Otto Körner”, Rostock University Medical Center, 18057 Rostock, Germany
7
Hearing4all Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2023, 15(3), 726; https://doi.org/10.3390/pharmaceutics15030726
Submission received: 10 January 2023 / Revised: 20 February 2023 / Accepted: 21 February 2023 / Published: 22 February 2023
(This article belongs to the Special Issue Personalized Pharmacotherapy and Individualized Delivering Strategies for ENT Applications)
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Abstract

Cochlear implants are well established to treat severe hearing impairments. Despite many different approaches to reduce the formation of connective tissue after electrode insertion and to keep electrical impedances low, results are not yet satisfying. Therefore, the aim of the current study was to combine the incorporation of 5% dexamethasone in the silicone body of the electrode array with an additional polymeric coating releasing diclofenac or the immunophilin inhibitor MM284, some anti-inflammatory substances not yet tested in the inner ear. Guinea pigs were implanted for four weeks and hearing thresholds were determined before implantation and after the observation time. Impedances were monitored over time and, finally, connective tissue and the survival of spiral ganglion neurons (SGNs) were quantified. Impedances increased in all groups to a similar extent but this increase was delayed in the groups with an additional release of diclofenac or MM284. Using Poly-L-lactide (PLLA)-coated electrodes, the damage caused during insertion was much higher than without the coating. Only in these groups, connective tissue could extend to the apex of the cochlea. Despite this, numbers of SGNs were only reduced in PLLA and PLLA plus diclofenac groups. Even though the polymeric coating was not flexible enough, MM284 seems to especially have potential for further evaluation in connection with cochlear implantation.
Keywords: dual drug delivery; cochlear implants; diclofenac; immunophilin inhibitor MM284; polymeric coating dual drug delivery; cochlear implants; diclofenac; immunophilin inhibitor MM284; polymeric coating

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MDPI and ACS Style

Behrends, W.; Wulf, K.; Raggl, S.; Fröhlich, M.; Eickner, T.; Dohr, D.; Esser, K.-H.; Lenarz, T.; Scheper, V.; Paasche, G. Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs. Pharmaceutics 2023, 15, 726. https://doi.org/10.3390/pharmaceutics15030726

AMA Style

Behrends W, Wulf K, Raggl S, Fröhlich M, Eickner T, Dohr D, Esser K-H, Lenarz T, Scheper V, Paasche G. Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs. Pharmaceutics. 2023; 15(3):726. https://doi.org/10.3390/pharmaceutics15030726

Chicago/Turabian Style

Behrends, Wiebke, Katharina Wulf, Stefan Raggl, Max Fröhlich, Thomas Eickner, Dana Dohr, Karl-Heinz Esser, Thomas Lenarz, Verena Scheper, and Gerrit Paasche. 2023. "Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs" Pharmaceutics 15, no. 3: 726. https://doi.org/10.3390/pharmaceutics15030726

APA Style

Behrends, W., Wulf, K., Raggl, S., Fröhlich, M., Eickner, T., Dohr, D., Esser, K.-H., Lenarz, T., Scheper, V., & Paasche, G. (2023). Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs. Pharmaceutics, 15(3), 726. https://doi.org/10.3390/pharmaceutics15030726

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