Micromechanical Device for Intracochlear Drug Delivery

摘要：耳蜗生理学和分子生物学的最新发展为治疗和预防感音神经性听力损失的新方法铺平了道路。这些进步最终将使数百万人受益。然而，为了实现这一目标，有必要开发一种安全可靠的机制，将生物活性化合物直接输送到内耳。这项合作研究的目标是设计和开发一种多功能的长期药物输送系统，用于治疗内耳疾病。德雷珀实验室的生物医学工程师在药物输送微系统的开发方面具有丰富的经验和专业知识，马萨诸塞州眼耳医院的临床医生和科学家在内耳生理学、药理学和耳科外科方面具有专业知识，他们将共同努力，设计、评估和完善治疗内耳疾病的药物输送系统。该装置将有广泛的应用，并有可能彻底改变听力损失的治疗。设计概念包括一个植入装置，适合人类的乳突腔。该装置包含一个外部可编程的植入泵，用于淋巴周围循环，一个插入鼓室的耳蜗内导管，一个储存和混合室，用于输送浓缩的生物活性化合物，以及用于检测和传输流量和压力信息的传感器。超小型化装置是一个完整的，长期（两年以上）的给药系统，包含治疗化合物，点药机构，控制电子设备和电源。它的发展利用了微流体和微机电系统（MEMS）技术的最新发展。在上一个项目期间，我们开发并测试了一种基于微流体的可穿戴药物输送设备，并在豚鼠模型中使用了一种新的往复输送模式进行了演示。更新提案的目标是：(1)通过建立和演示一个计算模型来开发整个耳蜗药物传递的精确控制，该模型将我们的药物传递的流体动力学方面纳入先前的溶质动力学模型，并转化为人类临床应用；(2)设计并构建可植入的微流控模块，包括微泵、流量传感器、流体分配网络和药物储存器；(3)设计和构建一个电子控制和电源模块，并与Aim 2的微流控模块集成，生产一个完全可植入的人体临床原型，首次应用于类固醇反应性自身免疫性内耳疾病。

DESCRIPTION (provided by applicant): Micromechanical Device for Intracochlear Drug Delivery GRANTING NIH INSTITUTE/CENTER: National Institute on Deafness and Other Communication Disorders (NIDCD) GRANT NUMBER: DC006848 ABSTRACT Recent developments in cochlear physiology and molecular biology have paved the way for new and innovative ways of treating and preventing sensorineural hearing loss. These advances will ultimately benefit millions of individuals. However, for this to occur, it will be necessary to develop a safe and reliable mechanism for delivering bioactive compounds directly to the inner ear. The goal of this collaborative research effort is to design and develop a versatile long-term drug delivery system for the treatment of inner ear disorders. Working together, biomedical engineers from Draper Laboratory with experience and expertise in the development of drug delivery microsystems, and clinicians and scientists from the Massachusetts Eye and Ear Infirmary with expertise in inner ear physiology, pharmacology and otologic surgery will engineer, evaluate and perfect a drug delivery system for the treatment of inner ear disorders. This device will have broad application and the potential for revolutionizing the treatment of hearing loss. The design concept includes an implanted device that fits within the mastoid cavity of humans. The device contains an externally-programmable, implanted pump to recirculate perilymph, an intracochlear catheter inserted into the scala tympani, a reservoir and mixing chamber for delivery of concentrated bioactive compounds, and sensors for detecting and transmitting flow and pressure information. The ultra-miniaturized device is a complete, long-term (two year and greater) delivery system, containing therapeutic compound, dispensing mechanism, control electronics, and power supply. Its development takes advantage of recent developments in microfluidics and MEMS (MicroElectroMechanical Systems) technologies. In the previous project period, we developed and tested a microfluidics-based, wearable drug delivery device and demonstrated it in a guinea pig model using a novel reciprocating delivery paradigm. The aims of the renewal proposal are to (1) Develop precision control of drug delivery throughout the cochlea by establishing and demonstrating a computational model that incorporates the fluid dynamic aspects of our drug delivery into previous models of solute kinetics and translates to human clinical applications; (2) Design and build an implantable microfluidic module including a micropump, flow sensor, fluid distribution network and drug reservoir; and (3) Design and build an electronic control and power module and integrate with the microfluidic module from Aim 2, producing a fully implantable prototype for human clinical use with the first application targeted at steroid-responsive autoimmune inner ear disease. PUBLIC HEALTH RELEVANCE: The ultimate goal of this project is to develop a device capable of delivering drugs directly to the inner ear of patients suffering from hearing loss and other diseases related to hearing and balance. The device will be implanted and will be programmable to deliver drugs locally to the inner ear, thereby avoiding side effects and problems with drugs reaching their target typically experienced by patients using oral or injected medications. The near-term application of the technology will be to develop an implantable drug delivery system for steroid- responsive autoimmune inner ear disease, avoiding the systemic side effects of steroids while treating the disease and preserving patients' hearing.