A polytherapy based approach to combat antimicrobial resistance using cubosomes

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dc.contributor.authorLai, XFen_AU
dc.contributor.authorHan, MLen_AU
dc.contributor.authorDing, Yen_AU
dc.contributor.authorChow, SHen_AU
dc.contributor.authorLe Brun, APen_AU
dc.contributor.authorWu, CMen_AU
dc.contributor.authorBergen, PJen_AU
dc.contributor.authorJiang, JHen_AU
dc.contributor.authorHsu, HYen_AU
dc.contributor.authorMuir, BWen_AU
dc.contributor.authorWhite, Jen_AU
dc.contributor.authorSong, JNen_AU
dc.contributor.authorShen, HHen_AU
dc.date.accessioned2022-05-05T23:59:32Zen_AU
dc.date.available2022-05-05T23:59:32Zen_AU
dc.date.issued2022-01-17en_AU
dc.date.statistics2022-04-22en_AU
dc.descriptionCitation on Springer page at https://doi.org/10.1038/s41467-022-28012-5 lists author Jiang as Jhih-hang. Correct spelling is Jhih-Hang as per ORCiD 0000-0002-1543-1634.en_AU
dc.description.abstractA 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”. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International Licence.en_AU
dc.description.sponsorshipThis work was supported by the NHMRC project grant APP1144652.en_AU
dc.identifier.citationLai, X., Han, M.-L., Ding, Y., Chow, S. H., Le Brun, A. P., Wu, C. M., Bergen, P. J., Jiang, J-h, Hsu, H.-Y., Muir, B. W., White, J., Song, J., Li, J. & Shen, H.-H. (2022). A polytherapy based approach to combat antimicrobial resistance using cubosomes. Nature Communications, 13(1), 1-12. doi:10.1038/s41467-022-28012-5en_AU
dc.identifier.issn2041-1723en_AU
dc.identifier.issue1en_AU
dc.identifier.journaltitleNature Communicationsen_AU
dc.identifier.pagination1-12en_AU
dc.identifier.urihttps://doi.org/10.1038/s41467-022-28012-5en_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/13133en_AU
dc.identifier.volume13en_AU
dc.language.isoenen_AU
dc.publisherSpringer Natureen_AU
dc.subjectDrugsen_AU
dc.subjectAntibioticsen_AU
dc.subjectDrug deliveryen_AU
dc.subjectMembranesen_AU
dc.subjectTherapyen_AU
dc.subjectMicrobial drug resistanceen_AU
dc.titleA polytherapy based approach to combat antimicrobial resistance using cubosomesen_AU
dc.typeJournal Articleen_AU
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