Development of a drug delivering round window niche implant for cochlear pharmacotherapy.

Autor: Wei C; Department of Otolaryngology, Hannover Medical School, Hannover, Germany.; Cluster of Excellence 'Hearing4all', German Research Foundation (DFG, 'Deutsche Forschungsgemeinschaft'), Hannover Medical School, Lower Saxony, Germany., Gao Z; Department of Otolaryngology, Hannover Medical School, Hannover, Germany.; Cluster of Excellence 'Hearing4all', German Research Foundation (DFG, 'Deutsche Forschungsgemeinschaft'), Hannover Medical School, Lower Saxony, Germany.; ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, China., Knabel M; Department of Otolaryngology, Hannover Medical School, Hannover, Germany., Ulbricht M; Center of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Greifswald, Germany., Senekowitsch S; Center of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Greifswald, Germany., Erfurt P; Department of Otolaryngology, Hannover Medical School, Hannover, Germany., Maggi N; Carl Zeiss GOM Metrology, Braunschweig, Germany., Zwick B; Carl Zeiss Industrielle Messtechnik GmbH, ZEISS Group, Essingen, Germany., Eickner T; Institute for Biomedical Engineering, University Medical Center Rostock, University of Rostock, Rostock, Germany., Matin-Mann F; Department of Otolaryngology, Hannover Medical School, Hannover, Germany., Seidlitz A; Center of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Greifswald, Germany.; Institute of Pharmaceutics and Biopharmaceutics, University of Duesseldorf, Duesseldorf, Germany., Lenarz T; Department of Otolaryngology, Hannover Medical School, Hannover, Germany.; Cluster of Excellence 'Hearing4all', German Research Foundation (DFG, 'Deutsche Forschungsgemeinschaft'), Hannover Medical School, Lower Saxony, Germany., Scheper V; Department of Otolaryngology, Hannover Medical School, Hannover, Germany.; Cluster of Excellence 'Hearing4all', German Research Foundation (DFG, 'Deutsche Forschungsgemeinschaft'), Hannover Medical School, Lower Saxony, Germany.
Jazyk: angličtina
Zdroj: Drug delivery [Drug Deliv] 2024 Dec; Vol. 31 (1), pp. 2392755. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1080/10717544.2024.2392755
Abstrakt: Background: There exists an unfulfilled requirement for effective cochlear pharmacotherapy. Controlled local drug delivery could lead to effective bioavailability. The round window niche (RWN), a cavity in the middle ear, is connected to the cochlea via a membrane through which drug can diffuse. We are developing individualized drug-eluting RWN implants (RNIs). To test their effectiveness in guinea pigs, a commonly used model in cochlear pharmacology studies, it is first necessary to develop guinea pig RNIs (GP-RNI).
Methods: Since guinea pigs do not have a RWN such as it is present in humans and to reduce the variables in in vivo studies, a one-size-fits-all GP-RNI model was designed using 12 data sets of Dunkin-Hartley guinea pigs. The model was 3D-printed using silicone. The accuracy and precision of printing, distribution of the sample ingredient dexamethasone (DEX), biocompatibility, bio-efficacy, implantability and drug release were tested in vitro . The GP-RNI efficacy was validated in cochlear implant-traumatized guinea pigs in vivo .
Results: The 3D-printed GP-RNI was precise, accurate and fitted in all tested guinea pig RWNs. DEX was homogeneously included in the silicone. The GP-RNI containing 1% DEX was biocompatible, bio-effective and showed a two-phase and sustained DEX release in vitro , while it reduced fibrous tissue growth around the cochlear implant in vivo .
Conclusions: We developed a GP-RNI that can be used for precise inner ear drug delivery in guinea pigs, providing a reliable platform for testing the RNI's safety and efficacy, with potential implications for future clinical translation.
Databáze: MEDLINE
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