Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms

Abstract

Purpose: Chronic infections of Candida albicans are characterised by the embedding of budding and entwined filamentous fungal cells into biofilms. The biofilms are refractory to many drugs and Candida biofilms are associated with ocular fungal infections. The objective was to test the activity of nanoparticulate amphotericin B (AmB) against Candida biofilms. Methods: AmB was encapsulated in the Molecular Envelope Technology (MET, N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan) nanoparticles and tested against Candida biofilms in vitro. Confocal laser scanning microscopy (CLSM) imaging of MET nanoparticles’ penetration into experimental biofilms was carried out and a MET-AmB eye drop formulation was tested for its stability. Results: MET-AmB formulations demonstrated superior activity towards C. albicans biofilms in vitro with the EC50 being ~30 times lower than AmB alone (EC50 MET-AmB = 1.176 μg mL−1, EC50 AmB alone = 29.09 μg mL−1). A similar superior activity was found for Candida glabrata biofilms, where the EC50 was ~10× lower than AmB alone (EC50 MET-AmB = 0.0253 μg mL−1, EC50 AmB alone = 0.289 μg mL−1). CLSM imaging revealed that MET nanoparticles penetrated through the C. albicans biofilm matrix and bound to fungal cells. The activity of MET-AmB was no different from the activity of AmB alone against C. albicans cells in suspension (MET-AmB MIC90 = 0.125 μg mL−1, AmB alone MIC90 = 0.250 μg mL−1). MET-AmB eye drops were stable at room temperature for at least 28 days. Conclusions: These biofilm activity findings raise the possibility that MET-loaded nanoparticles may be used to tackle Candida biofilm infections, such as refractory ocular fungal infections.

Developing nanosize carrier systems for Amphotericin‐B: A review on the biomedical application of nanoparticles for the treatment of leishmaniasis and fungal infections

“…[30,31] Another study from Alakkad et al, 2022 demonstrated powerful antifungal activity against biofilm-embedded (Candida albicans) cells. [32,33] These data indicated that the new formulation of Am-B (encapsulated in the Molecular Envelope Technology; N-palmitoyl-N-monomethyl-N, N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan) has a more antifungal activity compared to the drug alone in Candida biofilms. [33] These data indicated that a new formulation of Am-B can be more effective with minimal cytotoxicity for living cells.…”

“…[ 30,31 ] Another study from Alakkad et al., 2022 demonstrated powerful antifungal activity against biofilm‐embedded ( Candida albicans ) cells. [ 32,33 ] These data indicated that the new formulation of Am‐B (encapsulated in the Molecular Envelope Technology; N ‐palmitoyl‐ N ‐monomethyl‐ N , N ‐dimethyl‐ N , N , N ‐trimethyl‐6‐ O ‐glycolchitosan) has a more antifungal activity compared to the drug alone in Candida biofilms. [ 33 ] These data indicated that a new formulation of Am‐B can be more effective with minimal cytotoxicity for living cells.…”

Advances in Nanotechnology for Biofilm Inhibition

“…Polymeric NPs are nanosized particles composed of polymeric materials . The PNPs have numerous benefits over conventional antimicrobial agents, including enhanced drug stability, bioavailability, solubility, and sustained release. , They have also been extensively investigated for their anti-biofilm and antibacterial activity . Polymeric NPs can be prepared using several techniques such as solvent evaporation, emulsion, and nanoprecipitation.…”

“…Amphotericin B (AmB) polymeric NPs showed efficacy against Candida biofilms on polystyrene surfaces. Results showed that the polymeric NPs were ∼30× more efficient than AmB alone . Arias-Moliz and colleague showed that E. faecalis ATCC 29212 biofilms were inhibited by doxycycline-functionalized polymeric NPs on dentine material .…”

Progress of polymer-based strategies in fungal disease management: Designed for different roles

“…Although oral NPs resulted in lower AmB levels compared to intravenous liposomes in tested organs, they displayed similar efficacy in treatment of visceral leishmaniasis, aspergillosis, and systemic candidiasis in animal models ( Serrano et al., 2015 ). This formulation also exhibited increased anti-biofilm efficiency for better penetration ( Alakkad et al., 2022 ). Despite the massive designs in drug delivery systems, only a few studies have presented results of in vivo testing.…”