Otitis media (OM) is the most common specifically treated childhood disease in the United States. The widespread use of systemic antibiotics against a disease with such high prevalence and recurrence is believed to be partially responsible for the observed increase in resistance among pathogenic bacteria. Local, sustained delivery of antimicrobial agents to the site of infection allows for much higher local drug concentrations over time than could be achieved with systemic administration. Local delivery would also minimize systemic exposure, both to the patient and bacteria elsewhere in the body. Higher concentrations of antibiotics localized to the middle ear, in turn, could allow for a faster and more complete eradication of OM bacteria. Here we propose to develop a noninvasive trans-tympanic OM treatment based on a drug delivery system that will produce a sufficient flux of antibiotic across the tympanic membrane (TM) to be effective, and would also serve as a sustained release reservoir for that antibiotic. We hypothesize that chemical permeation enhancers (CPEs), such as are commonly and safely used in skin, will produce such a trans-tympanic flux. We further hypothesize that inclusion of an animo-amide local anesthetic (bupivacaine) will enhance that flux and treat otic pain associated with OM. We will develop a hydrogel- based system that will contain the CPE and antibiotic, and will maintain it in situ over an extended period.

Public Health Relevance

Middle ear infections are the most commonly treated infections in childhood. The purpose of this application is to develop a means of treating middle ear infections by applying a gel in the outer ear, once. Chemicals in the gel will help antibiotics cross the eardrum;the gel holds it in place. This approach could prevent antibiotic resistance and toxicity.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Exploratory/Developmental Grants (R21)
Project #
Application #
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Watson, Bracie
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital Boston
United States
Zip Code
Mizrahi, Boaz; Shankarappa, Sahadev A; Hickey, Julia M et al. (2013) A Stiff Injectable Biodegradable Elastomer. Adv Funct Mater 23:1527-1533
Khoo, Xiaojuan; Simons, Emmanuel J; Chiang, Homer H et al. (2013) Formulations for trans-tympanic antibiotic delivery. Biomaterials 34:1281-8
Mizrahi, Boaz; Khoo, Xiaojuan; Chiang, Homer H et al. (2013) Long-lasting antifouling coating from multi-armed polymer. Langmuir 29:10087-94
Tong, Rong; Kohane, Daniel S (2012) Shedding light on nanomedicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4:638-62
Epstein-Barash, Hila; Stefanescu, Cristina F; Kohane, Daniel S (2012) An in situ cross-linking hybrid hydrogel for controlled release of proteins. Acta Biomater 8:1703-9
Tong, Rong; Hemmati, Houman D; Langer, Robert et al. (2012) Photoswitchable nanoparticles for triggered tissue penetration and drug delivery. J Am Chem Soc 134:8848-55