Microfluidic Transtympanic Delivery System (MTDS)

描述（由申请人提供）：Vesticon将开发和测试一种经鼓室给药系统，用于改善普通前庭疾病在办公室环境中的应用。该系统包括一个新颖的插入系统和微流体泵技术，用于精确和灵活地控制前庭活性或耳蜗活性药物输送到中耳以吸收到内耳。微流体跨大西洋输送系统（MTDS）将是数字控制的，克服了当前方法/技术以及仍在开发中的技术的控制相关和实际限制。今天，经鼓室给药经常用于治疗各种常见的内耳疾病，如梅尼埃病、慢性迷路炎、突发性感音神经性听力损失和顽固性耳鸣，这些疾病影响着全世界数百万人。全世界大约每1000人中就有12人患有梅尼埃氏病，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。然而，尽管研究正在开发手术植入控制分娩的产品，但Vesticon认为，探索非手术控制分娩的解决方案具有重要价值。vestticon的MTDS有望克服现有技术的控制相关限制，以及目前正在开发的手术植入解决方案的实际限制。在第一阶段，我们将研究和开发一个面包板原型，用于受控的跨鼓室给药，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。我们将通过使用塑料耳和颞骨芯的医师测试器来评估可行性。在第二阶段，我们将以第一阶段的发现为基础，进行更先进的原型开发和进一步的测试。MTDS可以在PI的诊所和两个独立的测试点对动物或人类受试者进行测试，这将为该技术最终的后续III期开发、FDA批准和商业化做准备。

DESCRIPTION (provided by applicant): Vesticon will develop and test a transtympanic drug delivery system for improved treatment of common vestibular disorders for applications in the office-based setting. The system includes a novel insertion system and microfluidic pump technology for precise and flexible control of vestibulo-active or cochleo-active drugs delivered to the middle ear for absorption to the inner ear. The Microfluidic Transtympanic Delivery System (MTDS) will be digitally-controlled, overcoming control-related and practical limitations of current methods/technologies, as well as technologies still under development. Today, transtympanic drug delivery is regularly used to treat a variety 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. However, while research is underway to develop products for surgically-implanted controlled delivery, Vesticon believes there is significant value for exploring a non-surgical solution for controlled delivery. Vesticon's MTDS promises to overcome both the control-related limitations of existing technology as well as the practical limitations of surgically-implantable solutions now in development. In Phase I we will research 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. We will evaluate feasibility with physician testers using both plastic ears and temporal bone cores. During Phase II, we will build on Phase I findings for more advanced prototype development and further testing. MTDS could be tested on animals or human subjects at the PI's clinic and two independent beta sites, which will prepare this technology for eventual follow-on Phase III development, FDA clearance and commercialization. Public Health Relevance: The Microfluidic Transtympanic Delivery System (MTDS) will overcome shortcomings of current drug delivery methods to the inner ear for treatment of common vestibular problems. MTDS addresses both the control-related limitations of existing technology as well as the practical limitations of surgically-implantable solutions now in development. Meniere's disease, chronic labyrinthitis, sudden sensorineural hearing loss and intractable tinnitus impact millions of people worldwide.