Diclofenac-loaded PLGA nanoparticles downregulate LasI/R quorum sensing genes in pathogenic P. aeruginosa isolates.

Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that can gradually and consistently release drugs in a controlled manner. In this study, diclofenac sodium-loaded PLGA nanoparticles (DS-PLGA NPs) were produced by solvent evaporation technique and characterized using SEM, DLS, and zeta potential analyses. The antibacterial and antivirulence potential of DS-PLGA NPs against P. aeruginosa strains were examined using broth microdilution, crystal violet staining, hemolysis, and twitching quantification assays. Furthermore, the expression of the quorum sensing (QS) genes, lasI and lasR in P. aeruginosa strains after treatment with 1/2 MIC of DS-PLGA NPs was assessed using real-time PCR. SEM imaging of the synthesized NPs exhibited that the NPs have a spherical structure with a size range of 60-150 nm. The zeta potential of the NPs was - 15.2 mV, while the size of the particles in the aquatic environment was in a range of 111.5-153.8 nm. The MIC of prepared NPs against various strains of P. aeruginosa ranged from 4.5 to 9 mg/mL. Moreover, exposure of bacteria to sub-MIC of DS-PLGA NPs significantly down-regulated the expression of the lasI and lasR genes to 0.51- and 0.75-fold, respectively. Further, prepared NPs efficiently reduced the biofilm formation of P. aeruginosa strains by 9-27%, compared with the controls. Besides, DS-PLGA NPs showed considerable attenuation in bacterial hemolytic activity by 32-88% and twitching motility by 0-32.3%, compared with untreated cells. Overall, the present work exhibited the anti-QS activity of DS-PLGA NPs, which could be a safe and useful approach for treating P. aeruginosa infections.

In vitro and in silico assessment of anti-quorum sensing activity of Naproxen against Pseudomonas aeruginosa.

Serious infections caused by Pseudomonas aeruginosa are usually related to quorum sensing (QS)-dependent virulence factors. Hence, QS inhibition is a promising approach to overcoming P. aeruginosa infections. This study aimed to investigate the effect of naproxen on biofilm formation and QS-related virulence traits of P. aeruginosa. Furthermore, the anti-QS potential of naproxen was evaluated using real-time PCR and molecular docking analysis. Our findings supported the anti-QS activity of naproxen, as evidenced by down-regulation of the lasI and rhlI genes expression as well as the attenuation of bacterial protease, hemolysin, pyocyanin, biofilm, and motility. Additionally, the high binding affinity of naproxen with QS regulatory proteins was determined in the molecular docking simulation. Altogether, these findings suggest that naproxen has a promising potential in inhibiting QS-associated traits of P. aeruginosa.