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Evaluation of Antimicrobial Activities of Nanoparticles and Nanostructured Surfaces In Vitro
Published on: April 21, 2023
Biguanide-Derived Polymeric Nanoparticles Kill MRSA Biofilm and Suppress Infection In Vivo
Jianghua Li1, Wenbin Zhong1, Kaixi Zhang1
1Centre for Antimicrobial Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore.
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 -127 surfactant, annic acid (TA), and biguanide-based olymetformin (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.
Insights
Novel nanoparticles effectively kill drug-resistant MRSA biofilms. These FTP nanoparticles show superior efficacy and biocompatibility compared to existing treatments, offering a promising new therapy for MRSA infections.
Area of Science:
- Biomaterials Science
- Infectious Diseases
- Nanotechnology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat due to its resistance to antibiotics, exacerbated by biofilm formation.
- Biofilms shield bacteria, making them highly tolerant to conventional antimicrobial treatments.
- Developing effective strategies against MRSA biofilms is crucial for public health.
Purpose of the Study:
- To develop and evaluate a novel nanoparticle (NP) system for combating MRSA biofilm infections.
- To assess the efficacy and biocompatibility of these nanoparticles both in vitro and in vivo.
- To investigate the potential of these NPs as an alternative therapeutic approach for MRSA infections.
Main Methods:
- Fabrication of FTP NPs using Pluronic F-127, tannic acid, and polyhexamethylene biguanide (PHMB).
- In vitro assessment of FTP NPs' bactericidal activity against MRSA USA300 biofilms.
- In vivo evaluation using a murine excisional wound model and comparison with vancomycin treatment.
- In vitro cytotoxicity assays on mammalian cells and in vivo acute toxicity studies in mice.
Main Results:
- FTP NPs demonstrated significantly enhanced bactericidal activity against MRSA biofilms compared to PHMB alone, achieving a ~100-fold greater reduction in vitro.
- In vivo studies showed FTP NPs reduced MRSA USA300 biofilm bacteria by 1.8 log10, outperforming vancomycin (0.8 log10 reduction).
- FTP NPs exhibited lower cytotoxicity to mammalian cells than PHMB and showed no acute toxicity in mice at therapeutic doses.
Conclusions:
- Biguanide-based FTP NPs are highly effective against MRSA biofilms in vitro and in vivo.
- The developed NPs offer a promising, biocompatible alternative for treating challenging MRSA infections.
- FTP NPs represent a significant advancement in the development of novel antimicrobial agents.
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