Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200011, P. R. China.
Ear Institute, Shanghai Jiao Tong University School of Medicine, No.115, Jinzun Road, Shanghai, 200125, P. R. China.
Adv Sci (Weinh). 2024 Mar;11(12):e2305682. doi: 10.1002/advs.202305682. Epub 2024 Jan 15.
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.
目前尚无经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，这反映出缺乏明确的特定治疗靶点和有效的给药策略。研究表明，噪声创伤会导致小鼠耳蜗毛细胞（HCs）和螺旋神经节神经元（SGNs）中的烟酰胺腺嘌呤二核苷酸（NAD+）下调和线粒体功能障碍，而烟酰胺（NAM）补充的 NAD+可维持耳蜗线粒体的动态平衡，并防止体外和离体的神经兴奋毒性损伤，还可显著改善体内的 NIHL。为了解决由于耳朵中复杂的解剖学屏障和独特的清除途径导致的药物递送效率有限的问题，根据小鼠颞骨的解剖学拓扑结构，通过微计算机断层扫描和圆窗（RW）龛位的重建，开发了个性化的 NAM 包裹的多孔明胶甲基丙烯酰（PGMA@NAM），实现了水凝胶的原位植入、NAM 的持续释放以及在小鼠中的长期听觉保护。这项研究强烈支持将个性化的 PGMA@NAM 作为具有有效内耳递送的 NIHL 保护药物，为基于药物的 NIHL 治疗提供了新的思路。
