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Methicillin-resistan Staphylococcus aureus (MRSA) is a significant cause of drug-resistant infections. Its propensity to develop biofilms makes it especially resistant to conventional antibiotics. We present a novel nanoparticle (NP) system made from biocompatible  F  -127 surfactant,    annic acid (TA), and biguanide-based  p  olymetformin ( P MET) (termed FTP NPs), which can kill MRSA biofilm bacteria effectively in vitro and in vivo and which has excellent biocompatibility. FTP NPs exhibit biofilm bactericidal activity-ability to kill bacteria both inside and outside biofilm-significantly better than many antimicrobial peptides or polymers. At low concentrations (8-32 μg/mL) in vitro , FTP NPs outperformed PMET with ∼100-fold (∼2 log 10 ) greater reduction of MRSA USA300 biofilm bacterial cell counts, which we attribute to the antifouling property of the hydrophilic poly(ethylene glycol) contributed by F-127. Further, in an in vivo murine excisional wound model, FTP NPs achieved 1.8 log 10 reduction of biofilm-associated MRSA USA300 bacteria, which significantly outperformed vancomycin (0.8 log 10 reduction). Moreover, in vitro cytotoxicity tests showed that FTP NPs have less toxicity than PMET toward mammalian cells, and in vivo intravenous injection of FTP NPs at 10 mg/kg showed no acute toxicity to mice with negligible body weight loss and no significant perturbation of blood biomarkers. These biguanide-based FTP NPs are a promising approach to therapy of MRSA infections.

Biguanide-Derived Polymeric Nanoparticles Kill MRSA Biofilm and Suppress Infection In Vivo