Antibiofilm Synergistic Activity of Streptomycin in Combination with Thymol-Loaded Poly (Lactic-co-glycolic Acid) Nanoparticles against Isolates.

BACKGROUND

Thymol is an important component of essential oils found in the oil of thyme, is extracted mainly from , and was shown to act synergistically with streptomycin against biofilms. Additionally, thymol could be encapsulated into poly (lactic-co-glycolic acid) (PLGA) nanoparticles to overcome issues related to its low water solubility and high volatility. The present study aimed to investigate the antibiofilm activity of thymol-loaded PLGA nanoparticles (Thy-NPs) alone and in combination with streptomycin against biofilms of isolates.

METHODS

The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The antibiofilm activities were determined by the safranin dye assay. The synergistic effect of Thy-NPs with streptomycin was assessed by the checkerboard method. The kinetic study of the biofilm biomass and time-kill assay were further performed.

RESULTS

Thy-NPs exhibited the highest antibacterial activity against isolates, with MIC values ranging from 1 to 8 g/mL. Additionally, Thy-NPs showed the highest antibiofilm activity against isolates with minimal biofilm inhibitory concentration (MBIC) and minimal biofilm eradication concentration (MBEC) values ranging from 16 to 64 g/mL and from 32 to 128 g/Ml, respectively. The combination treatment combining Thy-NPs with streptomycin showed a synergistic effect against the inhibition of biofilm formation and eradication of biofilms of isolates with fractional inhibitory concentration index values ranging from 0.13 to 0.28. In addition, the MBIC and MBEC values of streptomycin against isolates were dramatically reduced (up to 128-fold) in combination with Thy-NPs, suggesting that Thy-NPs would enhance the antibiofilm activity of streptomycin. The biomass and time-kill kinetics analysis confirmed the observed synergistic interactions and showed the bactericidal activity of streptomycin in combination with Thy-NPs.

CONCLUSIONS

Our results indicate that the synergistic bactericidal effect between streptomycin and Thy-NPs could be a promising approach in the control of biofilm-associated infections caused by .