An alveolar macrophage-targeted ciprofloxacin polymeric prodrug improves survival in a murine model ofpneumonia.

Abstract

is a leading cause of both hospital- and community-acquired pneumonia. Nanomaterials have the potential to deliver antibiotics directly to sites of infection with improved pharmacokinetics and to avoid development of antimicrobial resistance. We previously demonstrated the use of alveolar macrophage (AM)-targeted polymeric prodrugs to prevent pneumonia in murine models caused by the facultative intracellular pathogensand. These fully synthetic mannose-tagged polymers engage with AM mannose receptors, permitting uptake and triggering intracellular ciprofloxacin release. Here we show that the AMs can also serve as a reservoir for releasing antibiotics to treat infections caused by a primarily extracellular bacterium. Aerosolized ciprofloxacin polymeric prodrugs significantly improved survival in a murine model ofpneumonia, reduced lung bacterial burden, lessened extent of lung injury, and prevented excessive neutrophilic inflammation.