Levofloxacin Inhalation Solution: Superior Efficacy and Minimized Hepatotoxicity Against Chronic Pseudomonas Aeruginosa-Induced Pulmonary Infection.

Abstract

Chronic Pseudomonas aeruginosa (PA)-induced pulmonary infection poses a severe global health threat due to limited therapeutic efficacy of conventional systemic administration and rising drug resistance. Inhalation therapy offers targeted pulmonary drug delivery but is hindered by suboptimal formulations and inefficient nebulizers. Herein, we developed a novel levofloxacin inhalation solution (LIS) and a custom-engineered vibrating-mesh nebulizer (PJ-102) as a synergistic drug-device combination for the treatment of chronic pulmonary infection. LIS exhibited excellent aerosolization performance with a 1.81-fold fine particle fraction of that of commercial jet nebulizer. And the superiority in treating chronic pulmonary infection was also proved by in vivo experiments. Additionally, LIS avoided the hepatotoxicity associated with systemic levofloxacin exposure, as evidenced by stable liver enzyme levels and normal hepatic pathology. This established LIS offered a promising therapeutic candidate for refractory PA-induced pulmonary infections and a valuable framework for advanced antimicrobial inhalation therapy development.