Pan Dorothy W, Kim Jinkyung, Quiñones Patricia M, Ricci Anthony J, Applegate Brian E, Oghalai John S
Caruso Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, CA 90033, USA.
Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA 94304, USA.
Int J Mol Sci. 2024 Dec 26;26(1):126. doi: 10.3390/ijms26010126.
Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea. We sought to assess PSCC infusion of gold NPs into the cochlea, including the NPs' distribution and effect on cochlear mechanics. We performed optical coherence tomography (OCT) imaging to monitor PSCC infusion of gold NPs into the cochlear chambers. OCT imaging demonstrated that the infusion specifically targeted the perilymphatic spaces within the cochlea. We assessed cochlear mechanics by using OCT vibrometry to measure sound-evoked movements of the basilar membrane. We found no changes in cochlear mechanics between measurements at baseline, after the PSCC canalostomy, immediately after the infusion, and 1 h after the infusion of gold NPs ( > 0.05, paired -test). These findings validate the PSCC infusion approach for perfusing the cochlear perilymphatic space with a nanoparticle delivery system. Thus, PSCC infusion of nanoparticles is a feasible therapeutic delivery technique for treating inner ear disorders while preserving residual cochlear function.
新型治疗性给药系统及内耳给药方法对于治疗听力损失和内耳疾病是必要的。然而,向被骨骼包裹且具有免疫豁免特性的内耳和耳蜗环境进行治疗性给药存在诸多障碍,这使得治疗内耳疾病具有挑战性。纳米颗粒(NPs)是一种可用于多种目的的治疗性给药系统,后半规管(PSCC)灌注是将其直接注入耳蜗的一种方法。我们试图评估通过PSCC向耳蜗灌注金纳米颗粒的情况,包括纳米颗粒的分布及其对耳蜗力学的影响。我们进行了光学相干断层扫描(OCT)成像,以监测金纳米颗粒通过PSCC向耳蜗腔的灌注情况。OCT成像表明,灌注特异性地靶向了耳蜗内的外淋巴间隙。我们通过使用OCT振动测量法来测量基底膜的声诱发运动,从而评估耳蜗力学。我们发现在基线测量、PSCC造瘘术后、灌注后即刻以及灌注金纳米颗粒1小时后的测量之间,耳蜗力学没有变化(配对t检验,P>0.05)。这些发现验证了通过PSCC灌注法利用纳米颗粒给药系统灌注耳蜗外淋巴间隙的可行性。因此,通过PSCC灌注纳米颗粒是一种在保留残余耳蜗功能的同时治疗内耳疾病的可行治疗性给药技术。