Wei Chunjiang, Gao Ziwen, Mau Robert, Eickner Thomas, Jüttner Gabor, Fiedler Nicklas, Seitz Hermann, Lenarz Thomas, Scheper Verena
Department of Otolaryngology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Cluster of Excellence "Hearing4all", German Research Foundation (DFG; "Deutsche Forschungsgemeinschaft"), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Pharmaceutics. 2024 Sep 23;16(9):1236. 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.
在人工耳蜗（CI）植入手术后保留残余听力仍然是一项关键挑战。已证明地塞米松（DEX）的应用对残余听力有积极影响。为了以局部和可控的方式递送DEX，可使用圆窗龛植入物（RNI），其允许药物通过圆窗膜扩散到耳蜗中。为了验证这一概念，通过模制制造了用于豚鼠的RNI作为CI创伤模型，并对其体外药物释放和体内生物学效应进行了测试。
使用含10% DEX的硅酮模制RNI。使用高效液相色谱（HPLC）随时间分析释放情况。14只成年豚鼠被随机分为两组（CI组或CI + RNI组）。所有动物均接受单侧CI电极插入创伤，随后进行CI植入。CI + RNI组还额外植入了含10% DEX的RNI。对动物进行4周的随访。进行听觉脑干反应和阻抗测量、微型计算机断层扫描（µCT）成像以及组织学检查以进行评估。
DEX在体外释放超过250天，最初有一个突释，随后随着时间推移释放速度减慢。比较CI组和CI + RNI组的听力阈值变化（从第0天到第28天），在32和40 kHz处观察到显著差异。CI + RNI组基底触点处的阻抗变化低于CI组。此外，与CI组相比，CI + RNI组下基底转的纤维化减少。
含10% DEX的RNI在抑制纤维化方面具有抗炎潜力，并且对高频听力保留有有益作用。
