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Polymeric micelles with anti-virulence activity against Candida albicans in a single- and dual-species biofilm

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Abstract

Infections caused by fungal biofilms with rapidly evolving resistance against the available antifungal agents are difficult to manage. These difficulties demand new strategies for effective eradication of biofilms from both biological and inert surfaces. In this study, polymeric micelles comprised of di-block polymer, poly-(ethylene glycol) methyl ether methacrylate and poly 2-(N,N-diethylamino) ethyl methacrylate polymer, P(PEGMA-b-DEAEMA), were observed to exhibit remarkable inhibitory effects on hyphal growth of Candida albicans (C. albicans) and C. tropicalis, thus preventing biofilm formation and removing existing biofilms. P(PEGMA-b-DEAEMA) micelles showed biofilm removal efficacy of > 40% and a 1.4-log reduction in cell viability of C. albicans in its single-species biofilms. In addition, micelles alone promoted high removal percentage in a mixed biofilm of C. albicans and C. tropicalis (~ 70%) and remarkably reduced cell viability of both strains. Co-delivery of fluconazole (Flu) and amphotericin B (AmB) with micelles showed synergistic effects on C. albicans biofilms (3-log reduction for AmB and 2.2-log reduction for Flu). Similar effects were noted on C. albicans planktonic cells when treated with the micellar system combined with AmB but not with Flu. Moreover, micelle-drug combinations showed an enhancement in the antibiofilm activity of Flu and AmB against dual-species biofilms. Furthermore, in vivo studies using Caenorhabditis elegans nematodes revealed no obvious toxicity of the micelles. Targeting morphologic transitions provides a new strategy for defeating fungal biofilms of polymorphic resistance strains and can be potentially used in counteracting Candida virulence.

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Acknowledgements

The authors thank Dr. Anton Blencowe’s laboratory for providing the (PEG-b-PCL) polymer.

Funding

The Australian Research Council Centre for Excellent in Convergent Bio-Nano Science and Technology (CBNS) has supported this project.

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Authors and Affiliations

  1. UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA, 5000, Australia

    Yassamin N. Albayaty, Nicky Thomas & Clive A. Prestidge

  2. Basil Hetzel Institute for Translational Health Research, Woodville South, Woodville, SA, 5011, Australia

    Yassamin N. Albayaty & Nicky Thomas

  3. ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, Australia

    Yassamin N. Albayaty, Nicky Thomas, Paulina D. Ramírez-García, Thomas P. Davis, John F. Quinn, Michael R. Whittaker & Clive A. Prestidge

  4. Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Pde, Parkville, VIC, 3052, Australia

    Paulina D. Ramírez-García, Thomas P. Davis, John F. Quinn & Michael R. Whittaker

  5. Department of Chemical Engineering, Faculty of Engineering, Monash University, Wellington Road, Clayton, VIC, 3800, Australia

    John F. Quinn

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  1. Yassamin N. Albayaty
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Contributions

YNA designed the study, conducted the experiments, and collected and analysed the data. YNA and NT wrote the manuscript. CAP and NT designed the research and reviewed the manuscript. PDR, TPD, JFQ, and MRW synthesized the polymer P(PEGMA-b-DEAEMA) and reviewed the manuscript. All authors have approved the final manuscript.

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Correspondence to Clive A. Prestidge.

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Albayaty, Y.N., Thomas, N., Ramírez-García, P.D. et al. Polymeric micelles with anti-virulence activity against Candida albicans in a single- and dual-species biofilm. Drug Deliv. and Transl. Res. 11, 1586–1597 (2021). https://doi.org/10.1007/s13346-021-00943-4

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