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Title: Biguanide-derived polymeric nanoparticles kill MRSA biofilm and suppress infection in vivo
Authors: Li, Jianghua
Zhong, Wenbin
Zhang, Kaixi
Wang, Dongwei
Hu, Jingbo
Chan-Park, Mary B.
Keywords: Engineering::Chemical engineering
Issue Date: 2020
Source: Li, J., Zhong, W., Zhang, K., Wang, D., Hu, J., & Chan-Park, M. B. (2020). Biguanide-derived polymeric nanoparticles kill MRSA biofilm and suppress infection in vivo. ACS Applied Materials & Interfaces, 12(19), 21231-21241. doi:10.1021/acsami.9b17747
Journal: ACS Applied Materials & Interfaces
Abstract: Methicillin-resistant 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, tannic acid (TA), and biguanide-based polymetformin (PMET) (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 log10) 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 log10 reduction of biofilm-associated MRSA USA300 bacteria, which significantly outperformed vancomycin (0.8 log10 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.
ISSN: 1944-8244
DOI: 10.1021/acsami.9b17747
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials & Interfaces, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
Fulltext Permission: embargo_20210520
Fulltext Availability: With Fulltext
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