Abstract
Drug-loaded nanoparticles (NPs) can improve infection treatment by ensuring drug concentration at the right place within the therapeutic window. Poly(lactic-co-glycolic acid) (PLGA) NPs are able to enhance drug localization in target site and to sustainably release the entrapped molecule, reducing the secondary effects caused by systemic antibiotic administration. We have loaded auranofin, a gold compound traditionally used for treatment of rheumatoid arthritis, into PLGA NPs and their efficiency as antibacterial agent against two Gram-positive pathogens, Streptococcus pneumoniae and Streptococcus pyogenes was evaluated. Auranofin-PLGA NPs showed a strong bactericidal effect as cultures of multiresistant pneumococcal strains were practically sterilized after 6 h of treatment with such auranofin-NPs at 0.25 μM. Moreover, this potent bactericidal effect was also observed in S. pneumoniae and S. pyogenes biofilms, where the same concentration of auranofin-NPs was capable of decreasing the bacterial population about 4 logs more than free auranofin. These results were validated using a zebrafish embryo model demonstrating that treatment with auranofin loaded into NPs achieved a noticeable survival against pneumococcal infections. All these approaches displayed a clear superiority of loaded auranofin PLGA nanocarriers compared to free administration of the drug, which supports their potential application for the treatment of streptococcal infections.