SBIR Phase I: Actively-Controlled Transtympanic (ACT) Drug Delivery System

这个小企业创新研究第一阶段项目建议展示和开发一种微创药物输送技术的原型，以满足对更实用和有效的经鼓膜药物输送系统的需求。该技术将专有的套管针导管与基于MEMS的微流体系统相结合，用于将前庭活性或耳蜗活性药物受控、持续地输送到中耳中，以吸收到内耳，用于耳鼻喉科、办公室环境中的常见听力和前庭疾病。该I期项目将利用初步研究，包括先前对人类颞骨的导管研究，以及围绕给药和微泵的研究，以设计和开发用于受控经鼓膜输送的试验板原型，包括：（a）用于改善药物灌注的插入技术和循环系统，以及（B）微流体技术，以最佳方案输送药物。将评价医师测试仪使用塑料耳和颞骨芯的可行性。该项目的更广泛的影响/商业潜力预计将更有效地治疗常见的内耳疾病，如梅尼埃？耳鸣是影响全球数百万人的一种常见的疾病。梅尼埃？耳鸣的疾病影响全世界1000个人中的大约12个，并且估计在美国有790万个人患有耳鸣。虽然经鼓膜分娩的优点已被普遍理解，但控制仍然是实现最佳和一致结果的主要挑战。受试者间甚至受试者内结果的广泛变异性已经提出了当前实践的主要问题，引入了可能导致永久性听力丧失和前庭功能减退或功能障碍的严重副作用，例如耳毒性。最近的研究表明，这些缺点可以在很大程度上克服与精确，受控，持续，低浓度递送到圆窗膜。虽然正在研究开发用于植入式受控或被动定时释放递送的产品，但推进非手术、侵入性较小和更主动受控的递送具有重要价值。预计该技术将克服市场上和开发中技术的有效性和实用性缺陷。

This Small Business Innovation Research Phase I project proposes to demonstrate and develop a prototype of a minimally-invasive drug delivery technology to address the need for a more practical and effective transtympanic drug delivery system. The technology combines a proprietary trocar catheter with a MEMS-based microfluidic system for controlled, sustained delivery of vestibulo-active or cochleo-active drugs into the middle ear for absorption to the inner ear, for common hearing and vestibular disorders for applications in the otolaryngology, office-based setting. This Phase I project will utilize preliminary research, including prior catheter studies with human temporal bones, as well as research around dosing and micropumping to design and develop a breadboard prototype for controlled, transtympanic delivery that includes: (a) insertion technology and circulating system for improved drug perfusion, and (b) a microfluidics technology to deliver drugs with the optimal protocol. The feasibility with physician testers using both plastic ears and temporal bone cores will be evaluated. The broader impact/commercial potential of this project is anticipated to be in more effective treatment of common inner ear diseases such as Meniere?s disease, chronic labyrinthitis, sudden sensorineural hearing loss and intractable tinnitus that impact millions of people worldwide. Meniere?s disease affects approximately 12 in 1000 individuals worldwide, and it is estimated that 7.9 million individuals in the U.S. suffer from tinnitus. Although the advantages of transtympanic delivery are generally understood, control remains a major challenge to realizing optimal and consistent outcomes. Wide inter-subject, and even intra-subject, variability in outcomes has presented a major problem with current practice, introducing the potential of serious side effects, such as oto-toxicity, that can lead to permanent hearing loss and vestibular hypofunction, or dysfunction. Recent studies indicate these shortcomings can be largely overcome with precise, controlled, sustained, low concentration delivery to the round window membrane. While research is underway to develop products for surgically-implanted controlled or passive time-release delivery, there is significant value for advancing a non-surgical, less invasive and more actively-controlled delivery. It is expected that this technology will overcome both efficacy and practical shortcomings of the technologies on the market and in development.