LAUSR

Abstract The potential use of liposomes for the pulmonary delivery of colistin has been hindered by their phospholipid membrane permeability resulting in a very low entrapment of colistin in the liposomes. To increase the entrapment capacity of colistin in liposomes, the anionic lipid sodium cholesteryl sulfate (Chol-SO4−) was used to enhance the electrostatic attraction between colistin and the lipid membrane. The resulting colistin-entrapped liposomes of Chol-SO4− (CCL) showed significantly greater entrapment efficiency in comparison with liposomes without Chol-SO4−. A time-kill kinetics study showed that colistin could redistribute from the liposomes into a new bacterial cell membrane to exert bactericidal activity. After intratracheal instillation, the CCL exhibited prolonged colistin retention in the lung with less colistin being transferred to the bloodstream and kidney, and the improved biodistribution further resulted in the enhanced therapeutic efficacy in a murine pulmonary Pseudomonas aeruginosa infection model compared with the colistin solution. These results highlight the suitability of applying an electrostatic attraction to entrap colistin in liposomes for pulmonary delivery by increasing colistin retention in the lung, while reducing the systemic exposure.