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.authorLi, Jen_AU
dc.contributor.authorShen, HHen_AU
dc.date.accessioned2024-08-26T02:55:14Zen_AU
dc.date.available2024-08-26T02:55:14Zen_AU
dc.date.issued2022-01-17en_AU
dc.date.statistics2024-08-26en_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”. © The Authors - Open Access CC-BY 4.0en_AU
dc.description.sponsorshipThe authors gratefully acknowledge the use of the facilities at the Monash X-ray Platform and Monash Micro Imaging (Monash University, Victoria, Australia). They thank Heidi Yu, Hasini Wickremasinghe and Zhi Ying Kho for their assistance in the in vitro experiment. The Australian Nuclear Science and Technology Organization (ANSTO) is gratefully acknowledged for providing the neutron research facilities (proposal numbers P6945 and P6451). H.-H.S. is an Australian NHMRC Career Development Research Fellow (GNT1106798) and J.L. is an NHMRC Principal Research Fellow (APP1157909). This work was supported by the NHMRC project grant APP1144652.en_AU
dc.format.mediumElectronicen_AU
dc.identifier.articlenumber343en_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), 343.doi:10.1038/s41467-022-28012-5en_AU
dc.identifier.issn2041-1723en_AU
dc.identifier.issue1en_AU
dc.identifier.journaltitleNature Communicationsen_AU
dc.identifier.urihttp://dx.doi.org/10.1038/s41467-022-28012-5en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15669en_AU
dc.identifier.volume13en_AU
dc.languageEnglishen_AU
dc.language.isoenen_AU
dc.publisherSpringer Natureen_AU
dc.subjectAntimicrobial agentsen_AU
dc.subjectDrugsen_AU
dc.subjectPathogensen_AU
dc.subjectTherapyen_AU
dc.subjectMicroscopyen_AU
dc.subjectNeutron reflectorsen_AU
dc.subjectLipidsen_AU
dc.subjectMembranesen_AU
dc.subjectPublic healthen_AU
dc.titleA polytherapy based approach to combat antimicrobial resistance using cubosomesen_AU
dc.typeJournal Articleen_AU
dcterms.dateAccepted2021-12-07en_AU
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