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Harnessing Neutrophils to Deliver Antibiotics Non-Invasively across the Tympanic Membrane for Otitis Media Treatment

Tang, W.; Ma, X.; Marlowe, C. M.; Liu, S. S.; Park, K.-W.; Chen, P.; Shu, H.; Yang, R.

2025-03-14 bioengineering
10.1101/2025.03.12.642923 bioRxiv
Show abstract

Acute otitis media (AOM) is a leading cause of pediatric antibiotic prescriptions. Systemic antibiotics cause side effects and antibiotic resistance, whereas local delivery of antibiotics (directly to the middle ear) is hindered by an impermeable biological barrier, the tympanic membrane (TM). Here, we report on a liposome that hitchhikes on neutrophils to deliver antibiotics to the site of infection. Distinct from previous immune-cell-based therapies, we enable neutrophil hitchhiking via a topical application of hydroxylated liposomes, thus bypassing the invasive neutrophil harvesting procedures. The hydroxylated liposomes are opsonized by the complement protein fragments and subsequently internalized by native neutrophils. A simple topical application completely cures AOM in an established chinchilla model. It points to a low-cost and non-invasive treatment for this prevalent disease, poised to reduce pediatric antibiotic usage.

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