Cross-Centre Activity

Bio-responsive nanocarriers for the eradication of bacterial and fungal biofilms

CBNS Chief Investigators involved: Professor Clive Prestidge, Professor Ben Boyd and Professor Tom Davis CBNS Researchers: Dr Mikey Whittaker, Dr John Quinn, Dr Paulina Ramírez-García, Dr Andrew Clulow and Dr Nicky Thomas CBNS PhD students: Ms Chelsea Thorn and Ms Yassamin Albayaty The UniSA-Monash cross-node research program aims to explore bacterial and fungal infection responsive nanocarriers for delivery of anti-biofilm agents directly to the site of action, increasing bioavailability and efficacy has continued to gain momentum and yielded positive outcomes.

Antifungal delivery via pH-responsive polymeric micelles

We have prepared and characterised pH-responsive micelles composed of the Monash team synthesised block copolymer poly[(N,N-diethylamino)ethyl methacrylate-block-polyethylene glycol methacrylate] (P[DEAEMA-b-PEGMA]) and demonstrated triggered release of the antifungal drug itraconazole within the low pH environment of Candida albican biofilms. Enhanced biofilm uptake, targeted release and improved delivery of itraconazole has resulted in a significantly increased death of fungal cells and biofilm eradication in comparison with non-encapsulated drug. We have successfully quantified the pH-controlled release and determined the mechanism of action. Furthermore, the anti-biofilm efficacy of pH sensitive micelles has been demonstrated on different fungal strains.

Liquid crystalline lipid nanocarriers for the triggered release of antimicrobial agents and anti-biofilm activity

Liquid crystalline lipid nanocarriers based on glyceryl monooleate (GMO) have been shown to effectively encapsulate a combination of large enzyme molecules (e.g. glycoside hydrolases that disrupt the extracellular matrix of biofilms) and small antibiotic molecules of varying hydrophilicities and to facilitate their improved penetration and triggered release within bacterial biofilms. The controlled release has been shown to be partially driven by the digestive action of lipase enzymes produced by bacteria within biofilms. Under biorelevant conditions, the liquid crystalline lipid nanocarriers facilitate significant enhancement in the stability of encapsulated biological antimicrobials, e.g. novel glycoside hydrolases. Additionally, the safety and efficacy of GMO cubosomes have been determined in various in vitro biological models and comparisons made with non-digestible liquid crystalline lipid nanocarriers and liposomes. Initial results are strongly positive and have encouraged ongoing investigations of the mechanisms of actions and application focused in vitro and in vivo studies.

KEY GOALS FOR 2020

1 Determine the biological response and effects of the pH-responsive micelles in various fungal biofilms and compare with other polymeric micelle systems. 2 Explore the performance of the pH-responsive micelles for delivery and efficacy improvement of other antimicrobials.

Yassamin Albayaty, Nicky Thomas, Paulina Ramírez-García, Thomas Davis, John Quinn, Michael Whittaker and Clive Prestidge, “pHResponsive copolymer micelles to enhance itraconazole efficacy against Candida albicans biofilms”, Journal of Materials Chemistry B, 8, 1672-1681, 2020

KEY GOALS FOR 2020

1 Advance anti-biofilm efficacy studies for a range of encapsulated antimicrobials (small and large molecules). 2 Gain further insight into the mechanisms of action.

Chelsea Thorn, Andrew Clulow, Ben Boyd, Clive Prestidge, Nicky Thomas, “Bacterial lipase triggers the release of antibiotics from digestible liquid crystal nanoparticles”, Journal of Controlled Release, 319, 168-182, 2020