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PH-Responsive copolymer micelles to enhance itraconazole efficacy against: Candida albicans biofilms

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dc.contributor.authorAl Bayaty, N.
dc.contributor.authorThomas, N.
dc.contributor.authorRamírez García, P.D.
dc.contributor.authorDavis, T.P.
dc.contributor.authorQuinn, J.F.
dc.contributor.authorWhittaker, M.R.
dc.contributor.authorPrestidge, C.A.
dc.date.issued2020
dc.description.abstractCandida albicans (C. albicans) is a common fungal pathogen causing both localised and systemic infections. The majority of these infections are promoted by biofilm formation, providing a protective matrix for the embedded fungi thereby evading the host immune defence and promoting resistance against anti-mycotic agents. In this study, pH-responsive micellar systems based on poly-(ethylene glycol) ethyl ether methacrylate (PEGMA) and poly 2-(diethylamino) ethyl methacrylate (DEAEMA) block-copolymers of P(PEGMA-b-DEAEMA) were specifically developed and loaded with the antifungal itraconazole (ICZ) to defeat C. albicans biofilms. The P(PEGMA-b-DEAEMA) di-block polymer micelles demonstrated a particle size of 55 ± 6 nm and high ICZ loads (12.0 ± 0.5% w/w). Within the biofilm's acidic microenvironment, tertiary amines of the pH-sensitive DEAEMA block are protonated, altering their conformation and enhancing the release of the micellar contents. Encapsulation of ICZ within micelles significantly enhanced the activity against C. albicans biofilms, with a significant reduction in the biofilm biomass (>50%) and in the number of viable cells (2.4 Log reduction) achieved, compared with the non-encapsulated ICZ. Confocal microscopy revealed a high affinity and accumulation of the micelles in C. albicans biofilms as a result of their size and specific electrostatic interaction, hence their improved activity. P(PEGMA-b-DEAEMA) based pH-responsive micelles offer significant potential as antifungal carriers for controlling Candida infections.
dc.identifier.citationJournal of Materials Chemistry B, 2020; 8(8):1672-1681
dc.identifier.doi10.1039/c9tb02586c
dc.identifier.issn2050-750X
dc.identifier.issn2050-7518
dc.identifier.urihttps://hdl.handle.net/11541.2/141493
dc.language.isoen
dc.publisherRoyal Society of Chemistry
dc.relation.grantARC
dc.rightsCopyright 2020 Royal Society of Chemistry
dc.source.urihttps://doi.org/10.1039/c9tb02586c
dc.subjectbiofilms
dc.subjectcandida albicans
dc.subjectfungal biofilms
dc.titlePH-Responsive copolymer micelles to enhance itraconazole efficacy against: Candida albicans biofilms
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916384109001831

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