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Purpose <p>Sustained and simultaneous delivery of antibiotics and flavonoids using nanoformulations represents an innovative therapeutic approach against drug-resistant bacteria. In the present study, we encapsulated levofloxacin and baicalin, a plant flavonoid, into chitosan nanoparticles using the ionic gelation technique and investigated the effects of the dual drug-loaded nanoparticles on virulence factors and toxin-producing genes in <i>P. aeruginosa</i> PAO1.</p> Methods <p>The physicochemical properties of Bai-Lvx-CsNPs were investigated using various characterization techniques. Furthermore, the effects of Bai-Lvx-CsNPs on <i>P. aeruginosa</i> growth, virulence traits, and toxin-associated genes were assessed.</p> Results <p>Characterization of Bai-Lvx-CsNPs revealed that the particles were spherical, with an average size of 69.26 ± 17.8&#xa0;nm. The release kinetics of baicalin and levofloxacin from Bai-CsNPs and Lvx-CsNPs demonstrated a gradual and sustained release profile. The highest growth inhibitory activity was observed for Bai-Lvx-CsNPs, with a MIC value of 1.56&#xa0;mg/mL. Furthermore, the MBC value of Bai-Lvx-CsNPs was determined to be 12.5&#xa0;mg/mL. In addition, cells treated with ½ MIC of dual-loaded nanoparticles exhibited the highest DNA leakage (24.08 ± 0.43 ng/µL). A reduction in LasA protease activity and pyocyanin production to 48.92 ± 5.72% and 13.33 ± 4.57%, respectively, confirmed the efficient effect of Bai-Lvx-CsNPs in suppressing secreted virulence factors. Treatment with the dually encapsulated nanoparticles significantly reduced swarming motility and the metabolic activity of bacterial biofilm to 1.7 ± 1.6% and 19.09 ± 0.33%, respectively. Furthermore, qPCR analysis showed the greatest reduction in the expression level of the <i>toxA</i> and <i>exoS</i> genes in <i>P. aeruginosa</i> PAO1 following treatment with Bai-Lvx-CsNPs, which decreased to 0.37 ± 0.05 and 0.45 ± 0.07 folds, respectively.</p> Conclusion <p>Collectively, these findings highlight the promising antivirulence activity of Bai-Lvx-CsNPs against <i>P. aeruginosa</i> PAO1. Bai-Lvx-CsNPs not only inhibit bacterial growth but also effectively suppress multiple virulence traits, highlighting their potential as a novel therapeutic strategy for the management <i>P. aeruginosa</i> infections. Future in vivo studies are warranted to validate their effectiveness and explore their applicability as alternative or adjunctive treatments against this pathogen.</p>

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Co-delivery of Baicalin and Levofloxacin Via Chitosan Nanoparticles Synergistically Inhibits Pseudomonas aeruginosa PAO1 by Targeting Virulence Factors and Toxin-Associated Genes

  • 期刊论文

  • 发表日期：

    2025年12月3日

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  • Ghazaleh Nikzad,
  • Reza Sadeghi,
  • Hossein Zahmatkesh,
  • Hojjatolah Zamani

摘要

Purpose

Sustained and simultaneous delivery of antibiotics and flavonoids using nanoformulations represents an innovative therapeutic approach against drug-resistant bacteria. In the present study, we encapsulated levofloxacin and baicalin, a plant flavonoid, into chitosan nanoparticles using the ionic gelation technique and investigated the effects of the dual drug-loaded nanoparticles on virulence factors and toxin-producing genes in P. aeruginosa PAO1.

Methods

The physicochemical properties of Bai-Lvx-CsNPs were investigated using various characterization techniques. Furthermore, the effects of Bai-Lvx-CsNPs on P. aeruginosa growth, virulence traits, and toxin-associated genes were assessed.

Results

Characterization of Bai-Lvx-CsNPs revealed that the particles were spherical, with an average size of 69.26 ± 17.8 nm. The release kinetics of baicalin and levofloxacin from Bai-CsNPs and Lvx-CsNPs demonstrated a gradual and sustained release profile. The highest growth inhibitory activity was observed for Bai-Lvx-CsNPs, with a MIC value of 1.56 mg/mL. Furthermore, the MBC value of Bai-Lvx-CsNPs was determined to be 12.5 mg/mL. In addition, cells treated with ½ MIC of dual-loaded nanoparticles exhibited the highest DNA leakage (24.08 ± 0.43 ng/µL). A reduction in LasA protease activity and pyocyanin production to 48.92 ± 5.72% and 13.33 ± 4.57%, respectively, confirmed the efficient effect of Bai-Lvx-CsNPs in suppressing secreted virulence factors. Treatment with the dually encapsulated nanoparticles significantly reduced swarming motility and the metabolic activity of bacterial biofilm to 1.7 ± 1.6% and 19.09 ± 0.33%, respectively. Furthermore, qPCR analysis showed the greatest reduction in the expression level of the toxA and exoS genes in P. aeruginosa PAO1 following treatment with Bai-Lvx-CsNPs, which decreased to 0.37 ± 0.05 and 0.45 ± 0.07 folds, respectively.

Conclusion

Collectively, these findings highlight the promising antivirulence activity of Bai-Lvx-CsNPs against P. aeruginosa PAO1. Bai-Lvx-CsNPs not only inhibit bacterial growth but also effectively suppress multiple virulence traits, highlighting their potential as a novel therapeutic strategy for the management P. aeruginosa infections. Future in vivo studies are warranted to validate their effectiveness and explore their applicability as alternative or adjunctive treatments against this pathogen.