Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs
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 c...
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Published in | Pharmaceutics Vol. 15; no. 3; p. 726 |
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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. |
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AbstractList | 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. |
Audience | Academic |
Author | Fröhlich, Max Esser, Karl-Heinz Scheper, Verena Raggl, Stefan Paasche, Gerrit Eickner, Thomas Wulf, Katharina Lenarz, Thomas Behrends, Wiebke Dohr, Dana |
AuthorAffiliation | 6 Department of Otorhinolaryngology, Head and Neck Surgery “Otto Körner”, Rostock University Medical Center, 18057 Rostock, Germany 2 Auditory Neuroethology and Neurobiology, Institute of Zoology, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany 5 MED-EL Research Center, 30625 Hannover, Germany 3 Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany 4 MED-EL Medical Electronics, 6020 Innsbruck, Austria 1 Department of Otolaryngology, Hannover Medical School, 30625 Hannover, Germany 7 Hearing4all Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany |
AuthorAffiliation_xml | – name: 1 Department of Otolaryngology, Hannover Medical School, 30625 Hannover, Germany – name: 6 Department of Otorhinolaryngology, Head and Neck Surgery “Otto Körner”, Rostock University Medical Center, 18057 Rostock, Germany – name: 5 MED-EL Research Center, 30625 Hannover, Germany – name: 2 Auditory Neuroethology and Neurobiology, Institute of Zoology, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany – name: 3 Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany – name: 7 Hearing4all Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany – name: 4 MED-EL Medical Electronics, 6020 Innsbruck, Austria |
Author_xml | – sequence: 1 givenname: Wiebke surname: Behrends fullname: Behrends, Wiebke organization: Auditory Neuroethology and Neurobiology, Institute of Zoology, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany – sequence: 2 givenname: Katharina orcidid: 0000-0002-9891-5174 surname: Wulf fullname: Wulf, Katharina organization: Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany – sequence: 3 givenname: Stefan surname: Raggl fullname: Raggl, Stefan organization: MED-EL Medical Electronics, 6020 Innsbruck, Austria – sequence: 4 givenname: Max surname: Fröhlich fullname: Fröhlich, Max organization: MED-EL Research Center, 30625 Hannover, Germany – sequence: 5 givenname: Thomas surname: Eickner fullname: Eickner, Thomas organization: Institute for Biomedical Engineering, Rostock University Medical Center, 18119 Rostock, Germany – sequence: 6 givenname: Dana surname: Dohr fullname: Dohr, Dana organization: Department of Otorhinolaryngology, Head and Neck Surgery "Otto Körner", Rostock University Medical Center, 18057 Rostock, Germany – sequence: 7 givenname: Karl-Heinz surname: Esser fullname: Esser, Karl-Heinz organization: Auditory Neuroethology and Neurobiology, Institute of Zoology, University of Veterinary Medicine Hannover Foundation, 30559 Hannover, Germany – sequence: 8 givenname: Thomas orcidid: 0000-0002-9307-5989 surname: Lenarz fullname: Lenarz, Thomas organization: Hearing4all Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany – sequence: 9 givenname: Verena orcidid: 0000-0001-8618-8793 surname: Scheper fullname: Scheper, Verena organization: Hearing4all Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany – sequence: 10 givenname: Gerrit surname: Paasche fullname: Paasche, Gerrit organization: Hearing4all Cluster of Excellence, Hannover Medical School, 30625 Hannover, Germany |
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Snippet | Cochlear implants are well established to treat severe hearing impairments. Despite many different approaches to reduce the formation of connective tissue... |
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SubjectTerms | Animal welfare Arrays Cochlear implants Connective tissue Deafness Dexamethasone Diclofenac Dosage and administration Drug delivery systems Drug therapy Drugs dual drug delivery Electrodes Evaluation immunophilin inhibitor MM284 Nonsteroidal anti-inflammatory drugs Patient outcomes polymeric coating Polymers Testing Transplants & implants Vehicles |
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Title | Dual Drug Delivery in Cochlear Implants: In Vivo Study of Dexamethasone Combined with Diclofenac or Immunophilin Inhibitor MM284 in Guinea Pigs |
URI | https://www.ncbi.nlm.nih.gov/pubmed/36986587 https://www.proquest.com/docview/2791700522/abstract/ https://search.proquest.com/docview/2792511043 https://pubmed.ncbi.nlm.nih.gov/PMC10058822 https://doaj.org/article/e1e2b384e9b644f589112f05f8b92e01 |
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