Development of a drug delivering round window niche implant for cochlear pharmacotherapy
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
Affiliations
Chunjiang Wei
Department of Otolaryngology, Hannover Medical School, Hannover, Germany
Ziwen Gao
Department of Otolaryngology, Hannover Medical School, Hannover, Germany
Martina Knabel
Department of Otolaryngology, Hannover Medical School, Hannover, Germany
Martin Ulbricht
Center of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Greifswald, Germany
Stefan Senekowitsch
Center of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Greifswald, Germany
Peter Erfurt
Department of Otolaryngology, Hannover Medical School, Hannover, Germany
Norman Maggi
Carl Zeiss GOM Metrology, Braunschweig, Germany
Bastian Zwick
Carl Zeiss Industrielle Messtechnik GmbH, ZEISS Group, Essingen, Germany
Thomas Eickner
Institute for Biomedical Engineering, University Medical Center Rostock, University of Rostock, Rostock, Germany
Farnaz Matin-Mann
Department of Otolaryngology, Hannover Medical School, Hannover, Germany
Anne Seidlitz
Center of Drug Absorption and Transport, Department of Biopharmacy and Pharmaceutical Technology, Institute of Pharmacy, University of Greifswald, Greifswald, Germany
Thomas Lenarz
Department of Otolaryngology, Hannover Medical School, Hannover, Germany
Verena Scheper
Department of Otolaryngology, Hannover Medical School, Hannover, Germany
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.
