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A polytherapy based approach to combat antimicrobial resistance using cubosomes

Xiangfeng Lai1, Mei-Ling Han2, Yue Ding1,3

  • 1Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, VIC, 3800, Australia.

Nature Communications
|January 18, 2022
PubMed

Insights

Polytherapy combining cubosomes and polymyxin demonstrates superior antimicrobial activity against Gram-negative "superbugs." This novel approach enhances membrane disruption, offering a promising alternative to traditional antibiotic treatments.

Area of Science:

  • Nanomedicine
  • Antimicrobial Resistance
  • Biotechnology

Background:

  • Declining antimicrobial drug pipeline and rising Gram-negative bacterial resistance necessitate novel therapeutic strategies.
  • Cubosomes and polymyxins exhibit distinct mechanisms for disrupting bacterial outer membranes.

Purpose of the Study:

  • To evaluate the antimicrobial efficacy of polymyxin-loaded cubosomes.
  • To explore polytherapy using cubosomes and polymyxin as an alternative treatment for Gram-negative pathogens.

Main Methods:

  • Investigated antimicrobial activity of polymyxin-loaded cubosomes and polytherapy (cubosomes + polymyxin).
  • Utilized confocal microscopy and neutron reflectometry to elucidate the mechanism of action.

Main Results:

  • Polytherapy demonstrated significantly enhanced antimicrobial activity compared to monotherapies.
  • A two-step mechanism was identified: initial outer membrane destabilization by polymyxin, followed by cubosome-induced disruption via lipid exchange.

Conclusions:

  • Nanoparticle-based polytherapy offers a potent strategy against antibiotic-resistant Gram-negative bacteria ('superbugs').
  • This approach presents a promising alternative to conventional drug-loaded lipid nanoparticles for combating resistant infections.

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