Combination therapy of curcumin and silver nanoparticles with enhanced anti-biofilm activity for treatment of endotracheal tube-associated infections

Ching-Yee Loo , Paul M. Young , Wing-Hin Lee, Daniela Traini, Rosalia Cavaliere, Cynthia B. Whitchurch, Ramin Rohanizadeh

Biofilm tolerance has become a serious clinical concern in the treatment of nosocomial pneumonia owing to the resistance to various antibiotics. There is therefore an urgent need to develop alternative antimicrobial agents or combination drug therapies that are effective via different mechanisms. Silver nanoparticles (AgNP) have been developed as anti-biofilm agent for the treatment of infections associated with the use of mechanical ventilations, such as endotracheal intubation. Meanwhile curcumin, a phenolic plant extract, has displayed natural anti-biofilm properties through the inhibition of bacterial quorum sensing systems. The aim of this study was to investigate the possible synergistic/additive interactions of AgNP and curcumin nanoparticles (Cur-NP) against both Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) microorganisms. The combination therapy against P. aeruginosa showed an additive effect with minimum inhibitory concentration (MIC) of 29.4 μg/mL. Similarly, it was found that the MIC of Cur-NP alone against S. aureus was 220 μg/mL, compared to 50 μg/mL for the combination therapy. Combination of AgNP and Cur-NP (termed as Cur-SNP) at ~100 μg/mL disrupted 50% of established bacterial biofilms (formed on microtiter plates). However, further increase in the concentration of Cu-SNP  failed to effectively eliminate the biofilms. To achieve the same effect, at least 500 μg/mL of Cur-NP alone was needed. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) revealed that
combination therapy (Cur-SNP) was the most potent to eradicate pre-formed biofilm compared to mono-drug therapy. These agents are also non-toxic to healthy lung cells (BEAS-2B). As a co-therapy, curcumin acts to inhibit biofilm re-assembly and production of virulence factors in biofilm while AgNP inactivates cells activities through binding with sulfur-based compounds.

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