Issue 8, 2020

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

Abstract

Candida 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.

Graphical abstract: pH-Responsive copolymer micelles to enhance itraconazole efficacy against Candida albicans biofilms

Article information

Article type
Paper
Submitted
16 noy 2019
Accepted
17 yan 2020
First published
20 yan 2020

J. Mater. Chem. B, 2020,8, 1672-1681

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

Y. N. Albayaty, N. Thomas, P. D. Ramírez-García, T. P. Davis, J. F. Quinn, M. R. Whittaker and C. A. Prestidge, J. Mater. Chem. B, 2020, 8, 1672 DOI: 10.1039/C9TB02586C

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