具备听力保存和内耳给药功能的电极设计

具备听力保存和内耳给药功能的电极设计
Electrode features for hearing preservation and drug delivery strategies


摘要：

背景/目的：
为避免人工耳蜗术后听力进一步降低的风险，需要优化电极设计以最大限度地减少电极插入和放置时产生的物理损伤。此外，必须对电极的设计进行优化，以适应无创手术的要求。术中和术后应用药物可以更好地保护听力。电极也能具备潜在的给药可能性。
方法：
本文所回顾的实验室研究和临床研究涉及：创伤最小化的电极设计参数的重要性；通过药物干预进一步减少创伤。通过文献回顾和实验室评估确定可用药物的范围。使用体外实验和动物模型研究植入的创伤性。目前正在开发三种给药设备，满足不同治疗方法的特殊需求。每一种给药方法通过模型和实验室试验进行评估，并对其概念进行了试管和体内研究。
结果：
目前的论据显示一种细的、有弹性的、之字布线的电极束具有优势。类固醇和细胞凋亡抑制剂(AM111)在动物试验中效果很好，并且两种都是很好的用于减少电极植入后听力损失的风险的药物。半慢性地塞米松洗脱，蜗内导管急性给药，和储存器长期扩散给药都显示为可行的。
结论：
一项通过设备优化和新技术发展，着眼于听力保存的项目已经产生了积极的效果和新的进一步发展、临床应用的概念。
Abstract

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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.