Журнал наномедицины и нанотехнологий

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Liposomal N-acetylcysteine Modulates the Pathogenesis of P. aeruginosa Isolated from the Lungs of Cystic Fibrosis Patient

Ahad Hasanin and Abdelwahab Omri

N-acetylcysteine (NAC) is a mucolytic agent with antimicrobial potential. We evaluated the antimicrobial activity of the free and liposomal NAC (F-NAC; L-NAC) against Pseudomonas aeruginosa. The minimum inhibitory concentrations (MIC), the minimum bactericidal concentrations (MBC) and the in vitro time kill studies of L-NAC were determined by broth-dilution method. Efficacy of the formulations on the production of N-acyl homoserine lactone molecules, virulence factors and motility were determined. Eradication of bacterial community within biofilms was assessed using the Calgary Biofilm Device. The L-NAC Cytotoxicity and anti-bacterial adhesion potential to human lung cells were examined using pulmonary A549 cell lines. The MIC of L-NAC was lower than the free drug (1250 mg/L and 5000 mg/L, respectively). MBC for L-NAC was 2500 mg/L compared to 5000 mg/L for F-NAC. L-NAC at 2500 mg/L killed bacteria in 2 h, whereas F-NAC exhibited the same effect at 5000 mg/L. Quorum sensing was significantly inhibited by L-NAC (P<0.001). At 1/8 MIC, L-NAC reduced the production of bacterial proteases significantly more than that of F-NAC at 1/4 MIC. L-NAC was also able to reduce the bacterial motility at eightfold lower concentration than F-NAC (P<0.001). As for biofilms, L-NAC provided 75% protection against biofilm formation, 90% reduction in the formed biofilms, and a 46% eradication effect on bacterial community within biofilms compared to treated biofilm with PBS (P<0.001). Finally, L-NAC at 2500 mg/L was safe to A549 cells, reduced bacterial adhesion by 15% compared to control (P<0.001). These data indicate that L-NAC formulation is more effective than F-NAC against P. aeruginosa and has the potential to improve therapeutic outcomes in CF patient.