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A polytherapy based approach to combat antimicrobial resistance using cubosomes

Author

Listed:
  • Xiangfeng Lai

    (Monash University)

  • Mei-Ling Han

    (Monash University)

  • Yue Ding

    (Monash University
    Monash University)

  • Seong Hoong Chow

    (Monash University)

  • Anton P. Brun

    (Australian Nuclear Science and Technology Organisation)

  • Chun-Ming Wu

    (Australian Nuclear Science and Technology Organisation
    National Synchrotron Radiation Research Center)

  • Phillip J. Bergen

    (Monash University)

  • Jhih-hang Jiang

    (Monash University)

  • Hsien-Yi Hsu

    (City University of Hong Kong
    Shenzhen Research Institute of City University of Hong Kong)

  • Benjamin W. Muir

    (CSIRO Manufacturing)

  • Jacinta White

    (CSIRO Manufacturing)

  • Jiangning Song

    (Monash University)

  • Jian Li

    (Monash University)

  • Hsin-Hui Shen

    (Monash University
    Monash University)

Abstract

A depleted antimicrobial drug pipeline combined with an increasing prevalence of Gram-negative ‘superbugs’ has increased interest in nano therapies to treat antibiotic resistance. As cubosomes and polymyxins disrupt the outer membrane of Gram-negative bacteria via different mechanisms, we herein examine the antimicrobial activity of polymyxin-loaded cubosomes and explore an alternative strategy via the polytherapy treatment of pathogens with cubosomes in combination with polymyxin. The polytherapy treatment substantially increases antimicrobial activity compared to polymyxin B-loaded cubosomes or polymyxin and cubosomes alone. Confocal microscopy and neutron reflectometry suggest the superior polytherapy activity is achieved via a two-step process. Firstly, electrostatic interactions between polymyxin and lipid A initially destabilize the outer membrane. Subsequently, an influx of cubosomes results in further membrane disruption via a lipid exchange process. These findings demonstrate that nanoparticle-based polytherapy treatments may potentially serve as improved alternatives to the conventional use of drug-loaded lipid nanoparticles for the treatment of “superbugs”.

Suggested Citation

  • Xiangfeng Lai & Mei-Ling Han & Yue Ding & Seong Hoong Chow & Anton P. Brun & Chun-Ming Wu & Phillip J. Bergen & Jhih-hang Jiang & Hsien-Yi Hsu & Benjamin W. Muir & Jacinta White & Jiangning Song & Jia, 2022. "A polytherapy based approach to combat antimicrobial resistance using cubosomes," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28012-5
    DOI: 10.1038/s41467-022-28012-5
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    References listed on IDEAS

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    1. Enrique R. Rojas & Gabriel Billings & Pascal D. Odermatt & George K. Auer & Lillian Zhu & Amanda Miguel & Fred Chang & Douglas B. Weibel & Julie A. Theriot & Kerwyn Casey Huang, 2018. "The outer membrane is an essential load-bearing element in Gram-negative bacteria," Nature, Nature, vol. 559(7715), pages 617-621, July.
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