Jolly C, Garnham C, Mirzadeh H, Truy E, Martini A, Kiefer J, Braun S
Adv Otorhinolaryngol. 2010;67:28-42. doi: 10.1159/000262594. Epub 2009 Nov 25.
BACKGROUND/AIMS: Reducing the risk of hearing loss after cochlear implantation requires optimization of the electrode array to minimize the physical trauma caused by insertion and placement. Furthermore, the electrode design must be optimized for atraumatic surgical approaches. Even greater levels of protection may be achieved by the use of a drug during and after implantation. The electrode array offers a potential vehicle for drug delivery.
This article reviews the laboratory and clinical data available thus far relating to the importance of electrode design parameters for trauma minimization, and the possibility of further reduction through pharmaceutical intervention. Candidate drugs were identified through literature review and laboratory evaluation. The most promising have been investigated in vitro and in animal models of implantation trauma. Three delivery devices are currently under development to satisfy the specific demands of different therapy regimes. The delivery profiles of each were evaluated through both modelling and bench testing and the concepts investigated in vitro and in vivo.
Current evidence favours a thin, flexible electrode array with wires in a zigzag shape. Steroids and an apoptosis inhibitor (AM111) performed well in animal models of electrode trauma and are both good drug candidates for reduction of the risk of hearing loss after implantation. Semi-chronic dexamethasone elution, acute drug delivery by intracochlear catheter, and longer-term delivery through diffusion from a reservoir were all shown to be feasible.
An extensive programme focussed on minimizing hearing loss through device optimization and the development of new technologies has yielded positive results and new concepts for further development and clinical application.
背景/目的:降低人工耳蜗植入后听力损失的风险需要优化电极阵列,以尽量减少插入和放置过程中造成的物理创伤。此外,电极设计必须针对无创手术方法进行优化。在植入期间及之后使用药物可能会提供更高水平的保护。电极阵列提供了一种潜在的药物递送载体。
本文回顾了目前可得的实验室和临床数据,这些数据涉及电极设计参数对最小化创伤的重要性,以及通过药物干预进一步降低创伤的可能性。通过文献综述和实验室评估确定了候选药物。最有前景的药物已在植入创伤的体外和动物模型中进行了研究。目前正在开发三种递送装置,以满足不同治疗方案的特定需求。通过建模和台架测试评估了每种装置的递送情况,并在体外和体内对这些概念进行了研究。
目前的证据支持采用带有之字形导线的薄而灵活的电极阵列。类固醇和一种凋亡抑制剂(AM111)在电极创伤的动物模型中表现良好,都是降低植入后听力损失风险的良好候选药物。半慢性地塞米松洗脱、通过鼓阶导管进行急性药物递送以及通过储库扩散进行长期递送均被证明是可行的。
一项专注于通过设备优化和新技术开发来最小化听力损失的广泛计划已经取得了积极成果,并为进一步发展和临床应用带来了新的概念。