Methylene Blue-Loaded Liposomal Nanocarriers Enhance the Efficacy of Photodynamic Therapy against Candida auris Biofilm

TL;DR

Liposomal nanocarriers improve photodynamic therapy against Candida auris biofilms by enhancing drug penetration and effectiveness.

Contribution

Proposes and validates liposomal nanocarriers to enhance methylene blue delivery for photodynamic therapy against C. auris biofilms.

Findings

MB-loaded liposomes eradicated planktonic C. auris cells at concentrations equivalent to free MB.

Liposomal MB reduced biofilm burden twice as effectively as free MB and decreased biofilm biomass by up to 37%.

Liposomal MB induced twice as much ROS production as free MB, causing greater oxidative damage to biofilms.

Abstract

Candida auris poses a
significant
healthcare challenge, particularly within immunosuppressed patients.
This pathogen can colonize the skin and develop biofilms associated
with increased antifungal drug resistance that are difficult to treat
with a limited antifungal repertoire. Some adjuvant treatments have
been investigated, such as photodynamic therapy (PDT), which employs
a photosensitizer (PS) irradiated by light. However, most PSs available
suffer from poor biofilm penetration. In this in vitro study, a nanocarrier
system was proposed as a possible strategy to facilitate the methylene
blue (MB) photosensitizer penetration into biofilm and improve PDT
action against C. auris. For this,
positively (MB-P) and negatively (MB-N) charged liposomes encapsulating
MB were successfully fabricated. In the PDT results, both liposome
formulations eradicated planktonic cells of C. auris at minimum fungicidal concentrations (MFC) equivalent to those of
free MB. MB-loaded liposomes showed enhanced penetration within biofilms
and reduced C. auris biofilm burden
∼2× more compared to free MB. Additionally, biofilm biomass
was reduced up to 37% with MB-loaded liposomes, while free MB only
achieved ∼3% reduction. Furthermore, PDT mediated by MB-P or
MB-N led to the production of reactive oxygen species (ROS) 2×
higher than free MB, leading to greater oxidative damage toward C. auris biofilms. Finally, the biocompatibility
of MB-loaded liposomes was examined against mammalian fibroblasts;
MB-loaded liposomes maintained ∼80% cell viability compared
to ∼58% viability for free MB. Promisingly, MB-P and MB-N liposomes
were able to enhance the in vitro activity of PDT on C. auris biofilms, inciting the development of in
vivo studies to validate their efficacy and safety.

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