Micromechanical Device for Intracochlear Drug Delivery

用于耳蜗内药物输送的微机械装置

• 批准号: 7784837
• 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/7784837
• 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)：用于耳内给药的微机械装置授予NIH研究所/中心：美国国家耳聋和其他沟通障碍研究所(NIDCD)资助号：DC006848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以百万计的个人受益。然而，要做到这一点，就必须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用于治疗内耳疾病的多功能长期给药系统。德雷珀实验室拥有药物输送微系统开发经验和专业知识的生物医学工程师，以及马萨诸塞州眼耳医院在内耳生理学、药理学和耳科外科方面拥有专业知识的临床医生和科学家将通力合作，设计、评估和完善用于治疗内耳疾病的药物输送系统。该设备将有广泛的应用和潜在的革命性的听力损失的治疗。这一设计理念包括一种植入人体乳突腔的装置。该设备包括一个外部可编程的植入式泵以使外淋巴液循环，一个插入鼓阶的耳内导管，一个用于输送浓缩生物活性化合物的储液器和混合室，以及用于检测和传输流量和压力信息的传感器。超小型设备是一个完整的、长期(两年或更长时间)的输送系统，包括治疗化合物、分配机构、控制电子设备和电源。它的开发利用了微流体和MEMS(微电子机械系统)技术的最新发展。在之前的项目期间，我们开发和测试了一种基于微流体的可穿戴药物输送装置，并使用一种新的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)通过建立和展示计算模型，将药物释放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，从而开发出对整个耳蜗的药物释放进行精确控制的计算模型；(2)设计和制造包括微泵、流量传感器、流体分配网络和药物储存库在内的植入式微流体模块；以及(3)设计和制造电子控制和电源模块，并与Aim 2的微流体模块集成，生产出供人类临床使用的完全可植入的原型，首次应用于类固醇反应性自身免疫性内耳疾病。 与公共卫生相关：该项目的最终目标是开发一种设备，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。该装置将被植入，并将被编程为将药物局部输送到内耳，从而避免副作用和药物到达目标时的问题，这是使用口服或注射药物的患者通常会经历的。该技术的近期应用将是开发一种可植入的药物输送系统，用于治疗类固醇反应性自身免疫性内耳疾病，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。