Development of a drug delivering round window niche implant for cochlear pharmacotherapy
| Autor: | Chunjiang Wei, Ziwen Gao, Martina Knabel, Martin Ulbricht, Stefan Senekowitsch, Peter Erfurt, Norman Maggi, Bastian Zwick, Thomas Eickner, Farnaz Matin-Mann, Anne Seidlitz, Thomas Lenarz, Verena Scheper |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Drug Delivery, Vol 31, Iss 1 (2024) |
| Druh dokumentu: | article |
| ISSN: | 10717544 1521-0464 1071-7544 |
| DOI: | 10.1080/10717544.2024.2392755 |
| Popis: | 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: | Directory of Open Access Journals |
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