Molded Round Window Niche Implant as a Dexamethasone Delivery System in a Cochlear Implant-Trauma Animal Model

• Published in: Pharmaceutics 2024-09, Vol.16 (9), p.1236
• Main Authors: Wei, Chunjiang, Gao, Ziwen, Mau, Robert, Eickner, Thomas, Jüttner, Gabor, Fiedler, Nicklas, Seitz, Hermann, Lenarz, Thomas, Scheper, Verena
• Format: Article
• Language: English
• Subjects: B cells; Central nervous system depressants; Chronic illnesses; cochlear implant surgery; Cochlear implants; Dexamethasone; Drug delivery systems; Drugs; Electrodes; Ethylenediaminetetraacetic acid; Foreign bodies; guinea pig; Hearing loss; High performance liquid chromatography; Hydrogels; Implants, Artificial; Inflammation; Investigations; local inner ear drug therapy; local pharmacotherapy; Methyl salicylate; Nanoparticles; Prosthesis; round window niche implant; Silicones; Surgery; Transplants & implants
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics16091236

Preserving residual hearing after cochlear implant (CI) surgery remains a crucial challenge. The application of dexamethasone (DEX) has been proven to positively affect residual hearing. To deliver DEX in a localized and controlled way, a round window niche implant (RNI), allowing drug diffusion via the round window membrane into the cochlea, may be used. To prove this concept, an RNI for guinea pigs as a CI-trauma model was manufactured by molding and tested for its drug release in vitro and biological effects in vivo. The RNIs were molded using silicone containing 10% DEX. Release was analyzed over time using high-performance liquid chromatography (HPLC). Fourteen adult guinea pigs were randomly assigned to two groups (CI or CI + RNI group). All animals received a unilateral CI electrode insertion trauma followed by CI insertion. The CI + RNI group was additionally implanted with an RNI containing 10% DEX. Animals were followed up for 4 weeks. Acoustically evoked auditory brainstem response and impedance measurement, micro-computed tomography (µCT) imaging, and histology were performed for evaluation. DEX was released for more than 250 days in vitro, with an initial burst followed by a slower release over time. Comparing the hearing threshold shift (from day 0 to day 28) of the CI and CI + RNI groups, significant differences were observed at 32 and 40 kHz. The impedance shift at basal contacts was lower in the CI + RNI group than in the CI group. Moreover, the fibrosis in the lower basal turn was reduced in the CI + RNI group in contrast to the CI group. The RNI containing 10% DEX has anti-inflammatory potential concerning fibrosis inhibition and has beneficial effects on hearing preservation at high frequencies.