Micromechanical Device for Intracochlear Drug Delivery

用于耳蜗内药物输送的微机械装置

• 批准号: 8074037
• 负责人: Jeffrey T. Borenstein
• 金额: $ 78.42万
• 依托单位: CHARLES STARK DRAPER LABORATORY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8074037
• 关键词: Adverse effects; Anatomy; Animal Testing; Animals; Autoimmune Process; Biocompatible; Biomedical Engineering; Catheters; Cavia; Charge; Clinical; Cochlea; Computer Simulation; Data; Data Reporting; Development; Device Designs; Devices; Disease; Disease remission; Drug Delivery Systems; Drug Transport; Ear; Electronics; Elements; Engineering; Equilibrium; Eye; Frequencies; Future; Genetic; Goals; Grant; Hearing; Hearing Tests; Housing; Human; Implant; Implantable Infusion Pumps; In Vitro; Individual; Institutes; Integrated Delivery Systems; Kinetics; Laboratories; Labyrinth; Liquid substance; Massachusetts; Mastoid process; Measurement; Methylprednisolone; Microfluidics; Microprocessor; Modeling; Modification; Molecular Biology; National Institute on Deafness and Other Communication Disorders; Natural regeneration; Operative Surgical Procedures; Oral; Patients; Perfusion; Perilymph; Pharmaceutical Preparations; Pharmacology; Physiology; Positioning Attribute; Power Sources; Preparation; Procedures; Pulsatile Flow; Pump; Radio; Research; Safety; Scala Tympani; Scientist; Sensorineural Hearing Loss; Staging; Steroids; Structure; System; Technology; Testing; Therapeutic; Time; Translating; United States National Institutes of Health; Weight; Work; abstracting; base; bone; clinical application; data modeling; design; design and construction; dosage; drug distribution; experience; hearing impairment; implantable device; implantation; in vitro testing; inner ear diseases; innovation; mechanical behavior; meter; microsystems; miniaturize; novel; operation; pressure; prevent; programs; prototype; public health relevance; research study; response; seal; sensor; simulation; solute

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.

描述（由申请人提供）：微机械装置用于耳蜗内药物输送授权NIH研究所/中心：国家耳聋和其他交流障碍研究所（NIDCD）授权号：DC 006848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的和创新的方法铺平了道路。这些进步最终将使数百万人受益。然而，为了实现这一点，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。来自德雷珀实验室的生物医学工程师在药物输送微系统开发方面具有经验和专业知识，来自马萨诸塞州眼耳医院的临床医生和科学家在内耳生理学，药理学和耳科手术方面具有专业知识，他们将共同设计，评估和完善用于治疗内耳疾病的药物输送系统。该设备将具有广泛的应用和彻底改变听力损失治疗的潜力。该设计概念包括一种植入式器械，可植入人体乳突腔。该装置包含一个外部可编程的植入泵，用于再循环外淋巴液，一个插入鼓阶的颅内导管，一个用于输送浓缩生物活性化合物的储存器和混合室，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（两年或更长时间）输送系统，包含治疗化合物、分配机制、控制电子设备和电源。它的开发利用了微流体和MEMS（微机电系统）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，并使用新型往复输送模式在豚鼠模型中进行了演示。更新提案的目的是（1）通过建立和证明一个计算模型，将我们的药物递送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，来开发整个耳蜗中药物递送的精确控制;（2）设计并构建了包括微泵、流量传感器、流体分配网络和药物储存器的可植入微流控模块;以及（3）设计和构建电子控制和电源模块，并与来自Aim 2的微流体模块集成，产生用于人类临床使用的完全可植入原型，其第一个应用针对类固醇响应性自身免疫性内耳疾病。 公共卫生关系：该项目的最终目标是开发一种能够将药物直接输送到患有听力损失和其他与听力和平衡有关的疾病的患者的内耳的设备。该装置将被植入，并将可编程以将药物局部输送到内耳，从而避免副作用和药物到达目标的问题，这些问题通常是使用口服或注射药物的患者所经历的。该技术的近期应用将是开发一种用于类固醇反应性自身免疫性内耳疾病的植入式药物输送系统，在治疗疾病和保护患者听力的同时避免类固醇的全身副作用。