RT Journal Article T1 Nanoemulsion-based colistin for pulmonary delivery: Enhanced antibacterial efficacy against Acinetobacter baumannii A1 Martínez Guitián, Marta A1 Sanjurjo Bouza, Lucía A1 Vázquez Ucha, Juan Carlos A1 Muras Mora, Andrea A1 Beceiro Casas, Alejandro A1 Crecente Campo, José A1 Alonso Fernández, María José AB 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. PB Springer YR 2026 FD 2026-03-30 LK https://hdl.handle.net/10347/46877 UL https://hdl.handle.net/10347/46877 LA eng NO Martínez-Guitián, M., Sanjurjo, L., Vázquez-Ucha, J.C., Muras, A., Beceiro, A., Crecente-Campo, J., & Alonso, M.J. (2026) Nanoemulsion-based colistin for pulmonary delivery: Enhanced antibacterial efficacy against Acinetobacter baumannii. Drug Delivery and Translational Research. https://doi.org/10.1007/s13346-026-02083-z NO Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work has received financial support from the Xunta de Galicia (Centro singular de Investigación de Galicia accreditation ED431G/2023/02) and the European Union (European Regional Development Fund—ERDF) and Competitive Reference Groups, Consellería de Educación e Ordenación Universitaria, Xunta de Galicia, Ref: ED431C 2021/17. DS Minerva RD 5 may 2026