Keynote
Trans-tympanic delivery of antibiotics

Otitis media is the most common reason U.S. children receive antibiotics. The requisite 7-10 day course of oral antibiotics can be challenging to deliver in children, entails potential systemic toxicity, and encourages selection of antimicrobial-resistant bacteria. We developed a drug delivery system which, when applied once to the tympanic membrane through the external auditory canal, delivers an entire course of antimicrobial therapy to the middle ear. A pentablock copolymer poloxamer 407-polybutylphosphoester (P407-PBP) was designed to flow easily during application then form a mechanically strong hydrogel on the tympanic membrane. FDA-approved chemical permeation enhancers within the hydrogel assisted flux of the antibiotic ciprofloxacin across the membrane. The hydrogel formulation containing 1% ciprofloxacin completely eradicated otitis media from non-typeable Haemophilus influenzae (NTHi) in 10 of 10 chinchillas, whereas only 62.5% of animals receiving 1% ciprofloxacin alone had cleared the infection by day 7. The hydrogel system was biocompatible in the ear, and ciprofloxacin was undetectable systemically (in blood) by high-performance liquid chromatography (HPLC), confirming local drug delivery and activity. This fast-gelling hydrogel could improve compliance, minimize side effects, and prevent systemic distribution of antibiotics in one of the most common paediatric illnesses, possibly minimizing development of antibiotic resistant bacteria.