Borkholder David A
Department of Electrical Engineering, Rochester Institute of Technology, Rochester, NY 14623, USA.
Curr Opin Otolaryngol Head Neck Surg. 2008 Oct;16(5):472-7. doi: 10.1097/MOO.0b013e32830e20db.
Treatment of auditory and vestibular dysfunction has become increasingly dependent on inner ear drug delivery. Recent advances in molecular therapy and nanotechnology have pushed development of alternate delivery methodologies involving both transtympanic and direct intracochlear infusions. This review examines recent developments in the field relevant to both clinical and animal research environments.
Transtympanic delivery of gentamicin and corticosteroids for the treatment of Meniere's disease and sudden sensorineural hearing loss continues to be clinically relevant, with understanding of pharmacokinetics becoming more closely studied. Stabilizing matrices placed on the round window membrane for sustained passive delivery of compounds offer more controlled dosing profiles than transtympanic injections. Nanoparticles are capable of traversing the round window membrane and cochlear membranous partitions, and may become useful gene delivery platforms. Cochlear and vestibular hair cell regeneration has been demonstrated by vector delivery to the inner ear, offering promise for future advanced therapies.
Optimal methods of inner ear drug delivery will depend on toxicity, therapeutic dose range, and characteristics of the agent to be delivered. Advanced therapy development will likely require direct intracochlear delivery with detailed understanding of associated pharmacokinetics.
听觉和前庭功能障碍的治疗越来越依赖于内耳给药。分子治疗和纳米技术的最新进展推动了包括经鼓膜和直接耳蜗内注射在内的替代给药方法的发展。本综述探讨了该领域在临床和动物研究环境方面的最新进展。
庆大霉素和皮质类固醇经鼓膜给药治疗梅尼埃病和突发性感音神经性听力损失在临床上仍然具有相关性，对其药代动力学的理解也得到了更深入的研究。置于圆窗膜上用于化合物持续被动给药的稳定基质比经鼓膜注射提供了更可控的给药方案。纳米颗粒能够穿过圆窗膜和耳蜗膜性分隔，可能成为有用的基因传递平台。通过向内耳递送载体已证明耳蜗和前庭毛细胞再生，为未来的先进治疗带来了希望。
内耳给药的最佳方法将取决于毒性、治疗剂量范围以及待递送药物的特性。先进治疗方法的开发可能需要直接耳蜗内给药，并详细了解相关的药代动力学。
