Personalized Porous Gelatin Methacryloyl Sustained-Release Nicotinamide Protects Against Noise-Induced Hearing Loss,Advanced Science

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Personalized Porous Gelatin Methacryloyl Sustained-Release Nicotinamide Protects Against Noise-Induced Hearing Loss
Advanced Science ( IF 14.3 ) Pub Date : 2024-01-15 , DOI: 10.1002/advs.202305682
Baoyi Feng _{1,

2,

3} , Tingting Dong _{2,

3,

4} , Xinyu Song ₅ , Xiaofei Zheng _{1,

2,

3} , Chenxi Jin _{1,

2,

3} , Zhenzhe Cheng _{1,

2,

3} , Yiqing Liu _{1,

2,

3} , Wenjie Zhang ₅ , Xueling Wang _{2,

3,

4} , Yong Tao _{1,

2,

3} , Hao Wu _{1,

2,

3}

Affiliation

There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM-encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro-computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained-release and long-term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug-based treatment of NIHL.

中文翻译：

个性化多孔明胶甲基丙烯酰缓释烟酰胺可预防噪音引起的听力损失

目前还没有美国食品和药物管理局批准的治疗噪声性听力损失（NIHL）的药物，反映出缺乏明确的具体治疗靶点和有效的给药策略。研究表明，噪音创伤会导致小鼠耳蜗毛细胞 (HC) 和螺旋神经节神经元 (SGN) 中的烟酰胺腺嘌呤二核苷酸 (NAD+) 下调和线粒体功能障碍，而补充烟酰胺 (NAM) 可以增强 NAD+ 的作用，从而维持耳蜗线粒体稳态并预防神经兴奋性毒性物质体外和离体损伤，也显着改善体内 NIHL。为了解决由于耳朵中复杂的解剖障碍和独特的清除途径而导致的药物输送效率有限的问题，基于小鼠颞骨的解剖地形，通过微计算机断层扫描和重建圆形结构，开发了个性化的 NAM 封装的多孔明胶甲基丙烯酰 (PGMA@NAM)。窗口（RW）生态位，实现水凝胶完全原位植入、NAM缓释和小鼠听觉长期保存。该研究有力支持个性化PGMA@NAM作为有效内耳递送的NIHL保护药物，为NIHL的药物治疗提供新的启示。

更新日期：2024-01-15

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