Microfluidic Transtympanic Delivery System (MTDS)

描述（由申请人提供）：Vesticon将开发和测试一种经鼓膜给药系统，用于改善在办公室环境中应用的常见前庭疾病的治疗。该系统包括一个新型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。微流体经鼓膜输送系统（MTDS）将采用数字控制，克服当前方法/技术以及仍在开发中的技术的控制相关和实际限制。如今，经鼓膜药物递送被定期用于治疗各种常见的内耳疾病，例如影响全球数百万人的梅尼埃病、慢性中耳炎、突发性感音神经性听力损失和顽固性耳鸣。美尼尔氏病影响全世界1000个人中的大约12个，并且据估计，美国有790万人患有耳鸣。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，这些缺点在很大程度上可以通过精确、可控、持续、低浓度递送到圆窗膜来克服。然而，虽然研究正在进行中，以开发产品的植入式控制交付，Vesticon认为，有显着的价值，探索非手术解决方案的控制交付。Vesticon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可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的经鼓膜给药的试验板原型，包括a）用于改善药物灌注的插入技术和循环系统;和B）微流体技术，以最佳方案给药。我们将与医生测试者一起使用塑料耳和颞骨芯评估可行性。在第二阶段，我们将在第一阶段研究结果的基础上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中心对动物或人类受试者进行测试，这将为最终的后续III期开发、FDA批准和商业化做好准备。 公共卫生相关性：微流体经鼓膜给药系统（MTDS）将克服目前药物递送方法的缺点，以治疗常见的前庭问题。MTDS既解决了现有技术的控制相关限制，也解决了目前正在开发的植入式解决方案的实际限制。梅尼埃病、慢性中耳炎、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。

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.