Development of a drug delivering round window niche implant for cochlear pharmacotherapy.
Drug Deliv
; 31(1): 2392755, 2024 Dec.
Article
en En
| MEDLINE
| ID: mdl-39166341
ABSTRACT
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.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Ventana Redonda
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Dexametasona
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Implantes Cocleares
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Sistemas de Liberación de Medicamentos
Idioma:
En
Revista:
Drug Deliv
/
Drug deliv
/
Drug delivery
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2024
Tipo del documento:
Article