Kresge Hearing Research Institute, Department of Otolaryngology - Head and Neck Surgery, Michigan Medicine, Ann Arbor, MI, USA.
Department of Otolaryngology, University of Colorado School of Medicine, Aurora, CO, USA.
Hear Res. 2018 Oct;368:127-135. doi: 10.1016/j.heares.2018.05.009. Epub 2018 May 17.
Drug delivery to the inner ear is an ideal method to treat a wide variety of otologic conditions. A broad range of potential applications is just beginning to be explored. New approaches combine principles of inner ear pharmacokinetics with emerging technologies of drug delivery including novel delivery systems, drug-device combinations, and new categories of drugs. Strategies include cell-specific targeting, manipulation of gene expression, local activation following systemic delivery, and use of stem cells, viral vectors, and gene editing systems. Translation of these therapies to the clinic remains challenging given the potential risks of intracochlear and intralabyrinthine trauma, our limited understanding of the etiologies of particular inner ear disorders, and paucity of accurate diagnostic tools at the cellular level. This review provides an overview of future methods, delivery systems, disease targets, and clinical considerations required for translation to clinical medicine.
内耳给药是治疗多种耳科疾病的理想方法。广泛的潜在应用才刚刚开始被探索。新方法将内耳药代动力学的原理与新兴的药物输送技术相结合,包括新型输送系统、药物-器械组合以及新类别的药物。策略包括细胞特异性靶向、基因表达的操纵、全身给药后的局部激活,以及使用干细胞、病毒载体和基因编辑系统。鉴于内耳创伤的潜在风险、我们对内耳疾病特定病因的有限了解以及细胞水平上准确诊断工具的缺乏,这些疗法向临床的转化仍然具有挑战性。本文综述了向临床医学转化所需的未来方法、输送系统、疾病靶点和临床注意事项。