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Ear infections are a common and painful occurrence in infants and toddlers. Oral antibiotics are often prescribed for a week to treat the condition, but these drugs can trigger side effects that disrupt treatment, which can lead to infection recurrence and antibiotic resistance. Now, researchers in ACS Nano a topical antibiotic gel that, applied once, cured middle ear infection within 24 hours in chinchillas.

“I often receive emails from parents asking when our formulation will be available, and I share their hope for a solution,” says Rong Yang, one of the research team leaders. “A single-dose treatment for middle ear infections represents a significant step forward toward reducing the burden on families and improving outcomes for young children.”

For middle ear infections, applying an antibiotic directly to the infected area rather than taking it orally could help reduce side effects like yeast infections and upset stomach. However, these infections occur behind the tympanic membrane (eardrum) — a structure that is impervious to most drugs. To overcome this problem, Yang, Wenjing Tang and colleagues encapsulated the antibiotic ciprofloxacin within liposomes, which have been used for delivery of other drugs because they interact with the cell structure of membranes like eardrums and skin to facilitate uptake.

Positively charged liposomes are widely considered better than negatively charged ones at transporting drugs across multilayered tissues like skin. In the current study, however, the researchers discovered that negatively charged liposomes were better able to deliver drugs across infected eardrums. Using mouse cells, they found this was because of the uptake of the liposomes by immune cells responding to the infection.

Yang’s team encapsulated the antibiotic ciprofloxacin in negatively charged liposomes and added them to a temperature-sensitive hydrogel to form an antibiotic salve. They then conducted experiments with chinchillas because the animal’s ears are like human ears in response to middle ear infections and treatment. They applied one of three formulations — ciprofloxacin in negatively charged liposomes in gel, ciprofloxacin in positively charged liposomes in gel, or ciprofloxacin in gel — to the eardrums of infected chinchillas and, after the gel solidified for sustained release, the antibiotic moved across the eardrum from the outer ear to the middle ear.

They found that all the ear-infected chinchillas receiving gel containing ciprofloxacin encapsulated in negatively charged liposomes were infection-free within 24 hours. Furthermore, the animals showed no eardrum inflammation or recurrence of infection during the seven days of treatment. In comparison, after seven days, only a portion of the animals receiving gel formulations with either free antibiotic (25%) or antibiotic encapsulated in positively charged liposomes (50%) were cleared of infection, and their eardrum inflammation was similar to that of untreated animals.

Yang, Tang and colleagues suggest that a single dose of treatment for middle ear infections could improve patient compliance and potentially reduce pediatric antibiotic usage, thereby improving patient care.

“I am most excited about the next stage of translating this technology from the lab to the clinic, as it has the potential to improve patient compliance, reduce antibiotic resistance, and ultimately transform how children receive antibiotics,” says Yang.

The authors acknowledge funding from the Hartwell Foundation and the National Institute on Deafness and Other Communication Disorders, part of the National Institutes of Health.

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