Moxifloxacin-Loaded Polymeric Nanoparticles for Overcoming Multidrug Resistance in Chronic Pulmonary Infections Caused by Pseudomonas aeruginosa

作者：Yujun Chen, Mao Xu, Jieyi Pan, Yuan Liao, Jintong Na, Pengyu Li, Yingying Sun, Shihui Yu, Yongxiang Zhao, Haiyan Hu · 发表于：ACS Applied Materials & Interfaces · 年份：2025 · DOI：10.1021/acsami.4c14991 · 被引用次数：15 · 研究领域：Antibiotic Resistance in Bacteria、Antimicrobial Peptides and Activities、Inhalation and Respiratory Drug Delivery

Pseudomonas aeruginosa ( P. aeruginosa ) infections are increasingly challenging due to their propensity to form biofilms and low outer membrane permeability, especially in chronically infected patients with thick mucus. P. aeruginosa exhibits multiple drug resistance mechanisms, making it one of the most significant global public health threats. In this study, we found that moxifloxacin (MXC) and antibacterial peptides (ε-poly- l -lysine, ε-PLL) exhibited a synergistic effect against multidrug-resistant P. aeruginosa (MDR- P. aeruginosa ). MXC was combined with ε-PLL to prepare lipase-responsive nanoparticles (MCIP/(PEG–PCL)/PLL NPs) with a weakly negative charge. The weakly negatively charged MCIP/(PEG–PCL)/PLL NPs demonstrated remarkable mucus and biofilm penetration capabilities, thereby overcoming one of the adaptive drug resistance mechanisms. MCIP/(PEG–PCL)/PLL NPs improved the outer and inner membrane permeability and inhibited the expression of the efflux pump MexAB-OprM gene in MDR- P. aeruginosa, thereby overcoming mechanisms of both intrinsic and acquired drug resistance. Meanwhile, the nanoparticles demonstrated an ability to reduce repeated infections with MDR- P. aeruginosa . Additionally, the bacterial burden in the lungs of mice treated with MCIP/(PEG–PCL)/PLL NPs was significantly lower than that in the MXC group, resulting in a 99% clearance rate. Notably, MCIP/(PEG–PCL)/PLL NPs showed no toxicity toward BEAS-2B cells or RAW 267.4 cells, nor did they advers...