Lajud Shayanne A, Nagda Danish A, Qiao Peter, Tanaka Nobuaki, Civantos Alyssa, Gu Rende, Cheng Zhiliang, Tsourkas Andrew, O'Malley Bert W, Li Daqing
*Department of Otorhinolaryngology-Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; †Department of Neuroscience, Baylor College of Medicine, Houston, Texas; and ‡Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, U.S.A.
Otol Neurotol. 2015 Feb;36(2):341-7. doi: 10.1097/MAO.0000000000000445.
A chitosan-hydrogel-based nanoparticle (nanohydrogel) delivery system can be used to deliver therapeutic biomaterials across the round window membrane (RWM) into the inner ear in a mouse model.
Delivering therapies to the inner ear has always been a challenge for the otolaryngologist. Advances in biomedical nanotechnology, increased understanding of the RWM diffusion properties, and discovery of novel therapeutic targets and agents, have all sparked interest in the controlled local delivery of drugs and biomaterials to the inner ear using nanoparticles (NPs).
Fluorescently-labeled liposomal NPs were constructed and loaded into a chitosan-based hydrogel to form a nanohydrogel, and in vitro studies were performed to evaluate its properties and release kinetics. Furthermore, the nanohydrogel was applied to the RWM of mice, and perilymph and morphologic analysis were performed to assess the NP delivery and distribution within the inner ear.
NPs with an average diameter of 160 nm were obtained. In vitro experiments showed that liposomal NPs can persist under physiologic conditions for at least two weeks without significant degradation and that the nanohydrogel can carry and release these NPs in a controlled and sustained manner. In vivo findings demonstrated that the nanohydrogel can deliver intact nanoparticles into the perilymphatic system and reach cellular structures in the scala media of the inner ear of our mouse model.
Our study suggests that the nanohydrogel system has great potential to deliver therapeutics in a controlled and sustained manner from the middle ear to the inner ear without altering inner ear structures.
基于壳聚糖水凝胶的纳米颗粒（纳米水凝胶）递送系统可用于在小鼠模型中通过圆窗膜（RWM）将治疗性生物材料递送至内耳。
向内耳递送治疗方法一直是耳鼻喉科医生面临的挑战。生物医学纳米技术的进展、对圆窗膜扩散特性的深入了解以及新型治疗靶点和药物的发现，都激发了人们对使用纳米颗粒（NPs）向内耳进行药物和生物材料的可控局部递送的兴趣。
构建荧光标记的脂质体纳米颗粒并将其装载到基于壳聚糖的水凝胶中以形成纳米水凝胶，并进行体外研究以评估其性质和释放动力学。此外，将纳米水凝胶应用于小鼠的圆窗膜，并进行外淋巴和形态学分析，以评估纳米颗粒在内耳中的递送和分布。
获得了平均直径为160 nm的纳米颗粒。体外实验表明，脂质体纳米颗粒在生理条件下可以持续至少两周而无明显降解，并且纳米水凝胶可以以可控和持续的方式携带和释放这些纳米颗粒。体内研究结果表明，纳米水凝胶可以将完整的纳米颗粒递送至外淋巴系统，并到达我们小鼠模型内耳中阶的细胞结构。
我们的研究表明，纳米水凝胶系统具有以可控和持续的方式从中耳向内耳递送治疗药物而不改变内耳结构的巨大潜力。
