Martínez Guitián, MartaSanjurjo Bouza, LucíaVázquez Ucha, Juan CarlosMuras Mora, AndreaBeceiro Casas, AlejandroCrecente Campo, JoséAlonso Fernández, María José2026-04-222026-04-222026-03-30Martínez-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-zhttps://hdl.handle.net/10347/46877Infections 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.engThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal article10.1007/s13346-026-02083-z2190-3948open access