Mustafa Rawand A, Wang Jiali, Xun Mengzhao, Rosenholm Jessica M, Wang Wuqing, Shu Yilai, Zhang Hongbo
ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, P. R. China.
Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, 20520, Finland.
Adv Sci (Weinh). 2025 Jun;12(24):e2407067. doi: 10.1002/advs.202407067. Epub 2024 Nov 21.
Local intratympanic drug delivery to the inner ear possesses significant otological clinical promise as cisplatin-induced hearing loss (CIHL) therapy, inducing significantly less side effects than systemic drug delivery. However, the multiple detoured barriers, round window membrane (RWM) and poorly controlled drug release hinder successful non-invasive drug delivery through intratympanic administration (IT). Here, a novel near-infrared (NIR) responsive nanocomposite functionalized with saponin, denoted gold nanorod@dexamethasone-mesoporous silica-saponin (AuNR@DEX-MS-saponin, NPs/DEX), is developed to enhance RWM permeation and to control the drug release spatiotemporally. First, the physiochemical properties and release profile of the synthesized nanocomposites are assessed, after which the biocompatibility of the nanocomposites and oto-protection against CIHL are shown in vitro and in vivo. The findings demonstrated that DEX is delivered to the inner ear with high efficiency through IT, due to the permeation enhancement effect of the nanocomposite. Moreover, the nanocomposite with low dose of DEX is highly effective in recovering CIHL, attenuating hair cell loss, and alleviating synaptic ribbon damage. These findings provide insight into NIR-responsive local delivery for inner ear illnesses.
作为顺铂诱导的听力损失（CIHL）的治疗方法，局部鼓室内药物递送对内耳具有显著的耳科临床前景，其副作用比全身药物递送少得多。然而，多个迂回的屏障、圆窗膜（RWM）以及难以控制的药物释放阻碍了通过鼓室内给药（IT）成功进行非侵入性药物递送。在此，开发了一种用皂苷功能化的新型近红外（NIR）响应纳米复合材料，即金纳米棒@地塞米松-介孔二氧化硅-皂苷（AuNR@DEX-MS-皂苷，NPs/DEX），以增强RWM渗透并时空控制药物释放。首先，评估合成纳米复合材料的理化性质和释放曲线，之后在体外和体内展示纳米复合材料的生物相容性以及对CIHL的耳保护作用。研究结果表明，由于纳米复合材料的渗透增强作用，DEX通过IT高效递送至内耳。此外，低剂量DEX的纳米复合材料在恢复CIHL、减轻毛细胞损失和缓解突触带损伤方面非常有效。这些发现为内耳疾病的近红外响应局部递送提供了见解。
