Perfluorocarbon nanoemulsion enables inhalable delivery of potent antimicrobial photosensitizer

Pulmonary antimicrobial photodynamic therapy (aPDT) faces site-specific drug delivery challenges that have hindered its translation into clinical studies. 1 Here, we present a novel nanoemulsion (NE) designed specifically for the treatment of respiratory infections, including a perfluorocarbon (PFC) core, pyropheophorbide (pyro) as a photosensitizer, and lung surfactant-like phospholipids in its composition. Pyro-based NEs have shown incredible preclinical success, with efficacy in vitro even in nanomolar concentrations, 2 while PFCs can improve drug delivery through inhalation and carry molecular oxygen. 3 This new pyro-PFC-NE has shown complete inactivation of S. aureus in nanomolar concentrations, in conditions that showed little to no toxicity against A549 lung epithelial and EA.hy926 endothelial cells. In addition, its size and photophysical properties are retained after nebulization and when exposed to lung surfactant. These results indicate that pyro-PFC-NE has significant potential for aPDT applications and is compatible with localized delivery to the lungs using nebulization.