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，用于改善办公室环境中常见前庭疾病的治疗。该系统包括一种新型的插入系统和微流体泵技术，用于精确和灵活地控制将前庭活性或耳蜗活性药物输送到中耳以吸收到内耳的药物。微流控经鼓室输送系统(MTDS)将由数字控制，克服当前方法/技术以及仍在开发中的技术与控制相关和实用的限制。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，这些疾病影响着全球数百万人。梅尼埃病在全球每1000人中约有12人受到影响，据估计，美国有790万人患有耳鸣。虽然人们普遍了解经鼓室分娩的优点，但控制仍然是实现最佳和一致结果的主要挑战。受试者之间，甚至受试者内，结果的广泛差异已经成为当前实践的一个主要问题，这带来了严重副作用的可能性，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，通过精确、可控、持续、低浓度的圆窗膜输送，这些缺点可以在很大程度上得到克服。然而，尽管正在研究开发用于手术植入的受控分娩的产品，但Vesticon相信探索一种用于受控分娩的非手术解决方案具有重大价值。Vesticon的MTDS承诺克服现有技术与控制相关的限制，以及目前正在开发的外科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种用于受控、经鼓室给药的面包板原型，其中包括a)用于改善药物灌流的插入技术和循环系统；以及b)以最佳方案输送药物的微流体技术。我们将评估内科医生同时使用塑料耳和颞骨骨芯的可行性。在第二阶段，我们将以第一阶段的研究结果为基础，进行更先进的原型开发和进一步测试。MTDS可以在PI的诊所和两个独立的测试点的动物或人类受试者身上进行测试，这将为最终的第三阶段开发、FDA批准和商业化准备这种技术。 公共卫生相关性：微流控跨鼓室给药系统(MTDS)将克服目前内耳药物给药方法的缺点，用于治疗常见的前庭问题。MTDS既解决了现有技术与控制相关的局限性，也解决了目前正在开发的外科植入性解决方案的实际局限性。梅尼埃病、慢性迷路炎、突发性感音神经性耳聋和顽固性耳鸣影响着全世界数百万人。

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.