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<p><i>Pseudomonas aeruginosa</i> (PA) biofilm-associated chronic lung infections pose a significant therapeutic challenge due to the limited penetration and efficacy of conventional antibiotics. In this study, we developed an innovative dry powder inhaler (DPI) formulation co-loading ciprofloxacin-encapsulated liposomes (CIP-Lips) and S-nitrosoglutathione (GSNO) using an ultrasonic spray-freeze-drying (USFD) technique. GSNO, a nitric oxide (NO) donor, promotes biofilm dispersion and induces bacterial phenotypic switching, thereby enhancing the accessibility of CIP-Lips to biofilm-embedded bacteria. Subsequently, CIP released from the liposomes exerts direct antibacterial activity. The combination of CIP-Lips and GSNO produces a synergistic “biofilm-disrupting and bactericidal” therapeutic effect, leading to effective biofilm eradication. The optimized DPI formulation exhibited satisfactory in vitro aerosol performance, with a fine particle fraction of 36.51 ± 0.49%, ensuring efficient lung deposition. In vitro evaluations further confirmed pronounced biofilm disruption and bactericidal efficacy. Furthermore, in a murine model of chronic pulmonary infection, the CIP-Lips/GSNO DPI significantly reduced the bacterial burden without observable systemic toxicity. This inhalable system represents a promising strategy for the treatment of PA biofilm-associated lung infections.</p>

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An inhalable dry powder co-delivery system of ciprofloxacin liposomes and S-nitrosoglutathione for synergistic treatment of Pseudomonas aeruginosa biofilm-associated pulmonary infections

  • 期刊论文

  • 发表日期：

    2026年4月17日

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  • Fang Ran,
  • Guihong Chai

摘要

Pseudomonas aeruginosa (PA) biofilm-associated chronic lung infections pose a significant therapeutic challenge due to the limited penetration and efficacy of conventional antibiotics. In this study, we developed an innovative dry powder inhaler (DPI) formulation co-loading ciprofloxacin-encapsulated liposomes (CIP-Lips) and S-nitrosoglutathione (GSNO) using an ultrasonic spray-freeze-drying (USFD) technique. GSNO, a nitric oxide (NO) donor, promotes biofilm dispersion and induces bacterial phenotypic switching, thereby enhancing the accessibility of CIP-Lips to biofilm-embedded bacteria. Subsequently, CIP released from the liposomes exerts direct antibacterial activity. The combination of CIP-Lips and GSNO produces a synergistic “biofilm-disrupting and bactericidal” therapeutic effect, leading to effective biofilm eradication. The optimized DPI formulation exhibited satisfactory in vitro aerosol performance, with a fine particle fraction of 36.51 ± 0.49%, ensuring efficient lung deposition. In vitro evaluations further confirmed pronounced biofilm disruption and bactericidal efficacy. Furthermore, in a murine model of chronic pulmonary infection, the CIP-Lips/GSNO DPI significantly reduced the bacterial burden without observable systemic toxicity. This inhalable system represents a promising strategy for the treatment of PA biofilm-associated lung infections.