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.
Yainax Medical has successfully demonstrated the feasibility in the development of a microfluidic system for local and sustained intratympanic drug delivery into the middle ear of a drug solution via a self-incising dual-lumen catheter. Local delivery of medication for treatment of inner ear diseases has evolved because of the limitations in efficacy and safety concerns associated with systemic therapy. Systemic therapy consists of dosing medication via oral, intravenous, or intramuscular routes with the intention of altering the inner ear function with significant limitation on the dosing rate. The approach detailed in our phase I final report focuses on sustained delivery of drug into the middle ear for absorption into the inner ear via the round window membrane, the primary transfer site of medication from the middle ear to the inner ear. From theoretical and experimental examinations of the delivery approach using the system developed during this phase, which was supported by animal studies, we concluded that delivery of drug into the middle ear for infusion through the round window membrane can be performed effectively and safely with careful execution of a series of protocols. These protocols are related to insertion of the catheter and delivery of the drug solution into the middle ear. However, if these protocols are not implemented correctly, then the end result could be a homogeneous distribution of drug within the middle ear, which may not be any different than what is currently being performed by bolus injection. An effective microfluidic system integrated with a dual-lumen catheter can provide ease of use and more effective infusion of drug through the round window membrane with little to no systemic side effects.
