Micromechanical Device for Intracochlear Drug Delivery

描述(由申请人提供)：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。该设备包括一个用于外淋巴液循环的外部可编程泵、一个通过耳蜗造口术插入鼓阶的鼓阶内导管、一个具有外部可编程输送浓缩生物活性化合物的混合室，以及用于检测和传输流量和压力信息的传感器。该系统的核心来自Draper团队在过去几年中设计、制造和测试的一种新型药物分配微系统。超小型设备是一个完整的、长期(一年或更长时间)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。建议的目的是：(1)开发适合化合物慢性、持续循环和外淋巴输注的内耳接口；(2)开发集成的、微机械的、液体控制系统；(3)制定外科手术程序并确定植入乳突腔的器械外形因素；(4)开发适合一系列候选疗法的植入式药物储存、填充和释放机构；(5)发展低功率控制电子、遥测和特定电源；(6)在初步动物实验中，使用原型设备向内耳输送化合物，以评估安全性和有效性。

DESCRIPTION (provided by applicant): 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 pump to recirculate perilymph, an intracochlear catheter inserted into the scala tympani through a cochleostomy, a mixing chamber with externally programmable delivery of concentrated bioactive compounds, and sensors for detecting and transmitting flow and pressure information. The core of the system is derived from a novel drug dispensing microsystem that the Draper team has designed, fabricated, and tested over the past several years. The ultra-miniaturized device is a complete, longterm (one year and greater) delivery system, containing therapeutic compound, dispensing mechanism, control electronics, and power supply. The aims of the proposal are to (1) develop an interface to the inner ear suitable for chronic, continuous recirculation of and infusion of compounds into perilymph; (2) develop an integrated, micromachined, fluid control system; (3) establish surgical procedures and determine device form factor constraints for implantation in the mastoid cavity; (4) develop an implantable drug storage reservoir, filling, and release mechanism appropriate for a range of candidate therapies; (5) develop low power control electronics, telemetry, and specify power source; and (6) evaluate safety and efficacy in preliminary animal experiments, using prototype devices to deliver compounds to the inner ear.