Topical Middle Ear Drug Delivery without Tympanic Membrane Puncture

DESCRIPTIONprovided by applicantThe ultimate goal of the project is to transform the treatment of chronic middle ear inflammations in childrenand to reduce the reliance on surgery and typmanostomy tubesTo do sowe are developing a first line topical non invasive treatment that can deliver therapy to the middle ear without tympanic membrane puncturesurgeryor general anesthesiaEar infections are the leading cause of child visits to pediatriciansApproximatelyof children with acute otitis mediaAOMprogress on to chronic otitis media with effusionCOMESurgery and tympanostomy tube placement under general anesthesia for treatment of recurrent AOM or COME is the most common pediatric surgical procedure requiring anesthesia in the United StatesThere are no effective non surgical treatments for COMEnor are there any medical treatments that block the progression of AOM to COMEOur system works by using magnetic forces to selectively deliver medical therapy across the intact tympanic membrane and into the middle earSystemic steroids have shown short term effectiveness for treatment of COMEbut long term steroid use has major drawbacks and risks and is not recommended clinically by the American Academies of PediatricsOur system enables concentrated topical delivery of steroidsand antibioticsto the middle earand will minimize symptoms associated with systemic steroid administrationIn this SBIR Phase I we will demonstrate that magnetic delivery of the steroid prednisolone resolves middle ear effusion and inflammationas compared to systemic steroids and to no treatment controlsThe first phase I aim will investigate the clearance of middle ear effusionby visual inspection and by quantitative measures of middle ear inflammationcytokinesinflammatory cell infiltrationetcAimwill assess hearing improvement by auditory brainstem responseABRmeasurementsAimwill verify that topical magnetic delivery reduces steroid concentration in blood serum as compared to systemic administrationAll three aims will be carried out in a recognized small animal model of COMEin C H HeJ miceThe number of animals in the study has been chosen to achieveconfidence hypothesis testing for all three aimsIn phase II we will examine a second recognized animal model of COMEe gchinchillaand will initiate safety and pharmacokinetic dynamicPK PDstudiesWe agree with reviewers that it important for our system to be able to treat both middle ear infections as well as middle ear inflammation and effusionWe are acutely aware of the clinical need to address both aspects and would like to note that we already have an active and funded grant from the FDAandapos s Pediatric Device Consortium at Childrenandapos s to show that our method can clear middle ear infectionsAs part of that grantwe have shown that our method can reliably clear middle ear infections in a recognized rodent model of acute otitis media PUBLIC HEALTH RELEVANCEOur overall goal is to improve the treatment of children with recurrent and chronic middle ear infectionsWe shall do so by using a proprietary non invasive drug delivery systemwhich will enable treatment of otitis media without the need for ear drum puncture or general anesthesia and its attendant risksIn this SBIR Phaseeffort we shall continue to focus on demonstrating our treatment for clearing middle ear inflammation and effusionWe agree with the reviewers that it is also critical to examine the effectiveness of our technology in clearing middle ear infectionsHoweverwe note that we already have a funded and ongoing grant from FDAandapos s Pediatric Device Consortium at Childrenandapos s Nationaland as part of that grant we have shown that we can reliably clear middle ear infections in a recognized rodent model of acute otitis media