内耳药物递送的研究进展与挑战：局限性与治疗前景

文献信息

中文摘要

引言： 听力损失是全球重大健康负担，年龄相关性听力损失影响全球数亿人。尽管治疗取得显著进展，但有效治疗仍受制于向内耳递送药物的挑战，内耳在解剖上难以进入且受到严密保护。
涵盖领域： 本叙述性综述基于对主要生物医学数据库的广泛检索，聚焦限制内耳药物递送的解剖和生理屏障、当前及新兴的给药途径，以及先进递送系统，包括水凝胶、纳米颗粒、微型装置和植入式平台。特别关注决定纳米载体性能的因素，以及临床转化的关键挑战，如物种依赖性药代动力学、生产可重复性、符合GMP的规模化生产和监管要求。通过PubMed、Embase、Web of Science和ClinicalTrials.gov检索了2001年至2026年间发表的研究。
专家意见： 尽管临床前创新迅速，临床转化仍不均衡。全身性硫代硫酸钠提供了最强的监管证据，证明具有临床意义的耳保护作用，而近期耳蜗内基因治疗为局部治疗建立了重要基准。对于纳米医学，进展将较少取决于平台新颖性，而更多取决于合理的结构-性质设计、可重复的耳蜗暴露、细胞分辨的生物分布、大型动物验证、符合GMP的生产、患者分层和临床试验设计。

英文摘要

INTRODUCTION: Hearing loss is a major global health burden, with age-related hearing loss affecting hundreds of millions of people worldwide. Despite significant therapeutic advances, effective treatment remains hampered by the challenge of delivering drugs to the inner ear, an anatomically inaccessible and tightly protected organ.
AREAS COVERED: This narrative review was based on an extensive search of major biomedical databases and focuses on the anatomical and physiological barriers that limit inner ear drug delivery, current and emerging administration routes, and advanced delivery systems, including hydrogels, nanoparticles, microdevices and implantable platforms. Particular attention is given to the factors governing nanocarrier performance and to the key challenges for clinical translation, such as species-dependent pharmacokinetics, manufacturing reproducibility, GMP-compatible scale-up and regulatory requirements. Studies published between 2001 and 2026 were identified through PubMed, Embase, Web of Science and ClinicalTrials.gov.
EXPERT OPINION: Despite rapid preclinical innovation, clinical translation remains uneven. Systemic sodium thiosulfate provides the strongest regulatory proof of clinically meaningful otoprotection, whereas recent intracochlear gene therapy establishes an important benchmark for localized treatment. For nanomedicine, progress will depend less on platform novelty than on rational structure-property design, reproducible cochlear exposure, cell-resolved biodistribution, large-animal validation, GMP-compatible manufacturing, patient stratification and clinical trial design.