A novel, quorum sensor-infused liposomal drug delivery system suppresses Candida albicans biofilms

H. M. H. N. Bandara, A. K. Hewavitharana, P. N. Shaw, H. D. C. Smyth, L. P. Samaranayake

Research output: Contribution to journalArticle (Academic Journal)

Abstract

In contrast to the plethora of antibacterial agents, only a handful of antifungals are currently available to treat Candida albicans biofilm-associated infections. Additional novel antibiofilm strategies to eliminate C. albicans biofilm infections are needed. This study aims to improve the efficacy of a widely used azole, fluconazole by co-delivering it with a Pseudomonas aeruginosa quorum sensing molecule (QSM), N-3-oxo-dodecanoyl-L-homoserine lactone (C12AHL) in a liposomal formulation. C12AHL is known to inhibit C. albicans’ morphological transition and biofilm formation. Four different formulations of liposomes with fluconazole (L-F), with C12AHL (L-H), with fluconazole and C12AHL (L-HF), and a drug-free control (L-C) were prepared using a thin-film hydration followed by extrusion method, and characterised. The effect of liposomes on colonising (90min-24h) and preformed (24h) C. albicans biofilms were assessed using a standard biofilm assay. Biofilm viability (XTT reduction assay), biomass (Safranin-O staining) and architecture (confocal laser scanning microscopy, CLSM) were determined. Similar efficiencies of fluconazole entrapment were noticed in L-HF and L-F (11.74% vs 10.2%), however, L-HF released greater quantities of fluconazole compared to L-F during 24h (4.27% vs 0.97%, P<0.05). The entrapment and release of C12AHL was similar for L-H and L-HF liposomes (33.3% vs 33% and 88.9% vs 92.3% respectively). L-HF treated colonising, and preformed biofilms exhibited >80%, and 60% reduction in their respective viabilities at a fluconazole concentration as low as 5.5µg/mL compared to 12% and 36%, respective reductions observed in L-F treated biofilms (P<0.05). CLSM confirmed biofilm disruption, lack of hyphae, and reduction in biomass when treated with L-HF compared to other liposomal preparations. Liposomal co-delivery of C12AHL and fluconazole appears to suppress C. albicans biofilms through efficacious disruption of the biofilm, killing of constituent yeasts, and diminishing their virulence at a significantly lower antifungal dose. Therefore, liposomal co-formulation of C12AHL and fluconazole appears to be a promising approach to improve the efficacy of this common triazole against biofilm-mediated candidal infections.
Original languageEnglish
Article number119096
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume578
Early online date30 Jan 2020
DOIs
Publication statusPublished - 30 Mar 2020

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Keywords

  • Candida albicans
  • fluconazole
  • N-(3-oxo-dodecanoyl)-L homoserine lactone
  • biofilms
  • antifungal resistance
  • liposomes

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