Propolis Nanoemulsion Enhance the Antimicrobial Effect on Multidrug-Resistant Strains of <i>Pseudomonas aeruginosa</i> in Combination with Ciprofloxacin

Background: Antimicrobial alternatives, including nanoparticles, are needed to combat bacteria as antibiotic resistance threatens global health. The aim of this research was to determine the antibacterial efficacy of a synthesized propolis nanoamulsion (PN) as a natural reducing agent and its synergistic effect in combination with ciprofloxacin (CP) against multidrug-resistant (MDR) P. aeruginosa biofilm. Methods: Scanning electron microscopy (SEM), dynamic light scattering (DLS) and zeta potential (ZP) were used to measure the mean particle size and nanoparticle size distribution. Iranian propolis (IP) was analyzed using gas chromatography-mass spectrometry (GC-MS). Antibacterial activity against MDR strains of P. aerugino sa was also evaluated. Furthermore, the synergistic in vitro effect of IP and PN combined with CP and the antiadhesion activity were evaluated using the checkerboard method and biofilm metabolic activity, respectively. Results: SEM, DLS and ZP revealed a size of 161.4 nm and a negative surface charge value of −37.4 mV. GC-MS analysis revealed the existence of four flavonoid compounds. This study showed that PN was more effective against MDR P. aeruginosa than IP with a minimum inhibitory concentration (MIC) value of 3.2-15 mg/mL. The combination of PN and CP had a synergistic effect, reducing the dosage of each compound and the time required to destroy the bacteria compared to using them separately. Furthermore, IP and PN suppressed the adhesion of MDR P. aeruginosa biofilm. Conclusions: According to the results, propolis nanoamulsion could enhance the antimicrobial effect, reduce the viability of bacteria and affect the biofilm formation of MDR P. aeruginosa . In combination with CP, it led to a stronger effect of the drug on the organism.