Nanoemulsion-based colistin for pulmonary delivery: Enhanced antibacterial efficacy against Acinetobacter baumannii

Infections caused by Acinetobacter baumannii, which frequently result in pneumonia and/or bacteraemia, represent a significant clinical challenge. Colistin, an antimicrobial peptide used as a last-resort therapy due to its high toxicity, is employed to treat severe infections, i.e. those caused by A. baumannii. The aim of this study was to develop a colistin-loaded nanoformulation (COL-NE) capable of targeting infected cells in the lung, thereby enhancing antibacterial efficacy while reducing toxicity. After screening multiple formulations, an optimized colistin nanoemulsion (COL-NE) was developed, exhibiting a particle size of 180 nm and a 1-4-fold reduction in MIC against A. baumannii compared to free colistin. The nanoemulsion also displayed significant antibiofilm activity, enhanced cellular penetration, and a 27-45% reduction in in vitro toxicity relative to colistin. Notably, following intratracheal administration, COL-NE improved the elimination of intracellular bacteria in macrophages through passive targeting while maintaining activity against extracellular bacteria. In a murine pneumonia model, COL-NE reduced lung bacterial burden by 2 log₁₀ CFU/mL compared with untreated controls and by 1.25 log₁₀ CFU/mL relative to colistin-treated mice. These findings highlight the potential of colistin-loaded nanoemulsions as a promising therapeutic strategy against A. baumannii infections, enhancing antibacterial efficacy while mitigating colistin-associated toxicity.