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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DC009986-01A1
Application #
7785685
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Watson, Bracie
Project Start
2010-01-22
Project End
2011-12-31
Budget Start
2010-01-22
Budget End
2010-12-31
Support Year
1
Fiscal Year
2010
Total Cost
$214,063
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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