A polytherapy based approach to combat antimicrobial resistance using cubosomes

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

28 Scopus Citations
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Author(s)

  • Xiangfeng Lai
  • Mei-Ling Han
  • Yue Ding
  • Seong Hoong Chow
  • Anton P. Le Brun
  • Chun-Ming Wu
  • Phillip J. Bergen
  • Jhih-hang Jiang
  • Benjamin W. Muir
  • Jacinta White
  • Jiangning Song
  • Jian Li
  • Hsin-Hui Shen

Detail(s)

Original languageEnglish
Article number343
Journal / PublicationNature Communications
Volume13
Online published17 Jan 2022
Publication statusPublished - 2022

Link(s)

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”.

Research Area(s)

Citation Format(s)

A polytherapy based approach to combat antimicrobial resistance using cubosomes. / Lai, Xiangfeng; Han, Mei-Ling; Ding, Yue et al.
In: Nature Communications, Vol. 13, 343, 2022.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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