Micromechanical Device for Intracochlear Drug Delivery

用于耳蜗内药物输送的微机械装置

• 批准号: 8292074
• 负责人: Jeffrey T. Borenstein
• 金额: $ 77.97万
• 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/8292074
• 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）：授果内药物交付授予NIH研究所/中心的微机械设备：美国耳聋和其他沟通障碍研究所（NIDCD）赠款编号：DC006848 dc006848摘要的摘要，在处理新颖和创新的方式治疗和预防传感器的新方法方面的抽象最新进展已经付出了。这些进步最终将使数百万个人受益。但是，为此，有必要开发一种安全可靠的机制，将生物活性化合物直接传递到内耳。这项协作研究工作的目的是设计和开发一种用于治疗内耳疾病的多功能长期药物输送系统。从Draper实验室的生物医学工程师共同努力，具有在药物输送微型系统开发方面的经验和专业知识，以及来自马萨诸塞州的眼睛和耳朵医务人员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，将工程，评估和完美的药物输送系统，以治疗内耳耳朵分离的药物。该设备将具有广泛的应用，并具有彻底改变听力损失治疗的潜力。设计概念包括适合人类乳突腔的植入设备。该设备包含一个外部编程的，植入的泵，用于再循环Perilymph，一个插入Scala Tympani，储层和混合室以输送浓缩生物活性化合物的储层和混合室，以及用于检测和传输流量和压力信息的传感器。超量化设备是一个完整的，长期的（两年及更高）的输送系统，包含治疗化合物，分配机制，控制电子和电源。它的开发利用了微流体和MEM（微电力系统）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装置，并使用新颖的往复式递送范式在豚鼠模型中证明了这一点。续签建议的目的是（1）通过建立和证明一种计算模型，将药物递送的流体动态方面纳入先前的溶质动力学模型，并转化为人类的临床应用； （2）设计和建立一个可植入的微流体模块，包括微型蛋白会，流动传感器，流体分布网络和药物储层； （3）设计和构建电子控制和功率模块，并与AIM 2的微流体模块集成，从而产生一个完全可植入的原型，用于人类临床用途，其针对类固醇反应性自身免疫性内耳病。 公共卫生相关性：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的患者的内耳和其他与听力和平衡有关的疾病的装置。该设备将被植入，并且可以编程，以将药物局部运送到内耳，从而避免使用口服或注射药物的患者通常会经历的药物达到其靶标的副作用和问题。该技术的近期应用将是开发一种可植入的药物输送系统，用于类固醇反应性自身免疫性内耳疾病，避免了类固醇的全身副作用，同时治疗疾病并保留患者的听力。