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旨在展示和开发一种微创给药技术的原型，以满足对更实用、更有效的跨腹腔给药系统的需求。该技术将专利套管针导管与基于mems的微流体系统相结合，可控制、持续地将前庭活性或耳蜗活性药物输送到中耳，以吸收到内耳，用于耳鼻喉科和办公室环境中的常见听力和前庭疾病。这个第一阶段的项目将利用初步的研究，包括先前对人类颞骨的导管研究，以及对剂量和微泵的研究，来设计和开发一个受控的、经鼓室输送的breadboard原型，其中包括：(a)插入技术和循环系统，以改善药物灌注；(b)微流体技术，以最佳方案输送药物。将评估使用塑料耳和颞骨核的医师测试器的可行性。预计该项目的更广泛影响/商业潜力将是更有效地治疗常见内耳疾病，如梅尼埃尔？S疾病、慢性迷路炎、突发性感音神经性听力损失和顽固性耳鸣影响着全世界数百万人。美尼尔综合症?全世界大约每1000人中就有12人患有耳鸣。据估计，美国有790万人患有耳鸣。虽然人们普遍了解跨腹膜输送的优势，但控制仍然是实现最佳和一致结果的主要挑战。广泛的受试者之间，甚至是受试者内部，结果的可变性已经成为当前实践中的一个主要问题，引入了严重副作用的可能性，例如耳毒性，可能导致永久性听力损失和前庭功能减退或功能障碍。最近的研究表明，这些缺点可以通过精确、可控、持续、低浓度的输送到圆窗膜上来很大程度上克服。虽然研究正在开发手术植入控制或被动缓释输送的产品，但推进非手术、更少侵入性和更主动控制的输送具有重要价值。预计该技术将克服市场上和开发中的技术的功效和实际缺点。

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.