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Published on: September 16, 2022
Amphotericin B Polymer Nanoparticles Show Efficacy against Candida Species Biofilms
Abdulghani Alakkad1, Paul Stapleton1, Corinna Schlosser1
1UCL School of Pharmacy, University College London (UCL), 29-39 Brunswick Square, London WC1N 1AX, UK.
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.
Insights
Nanoparticulate amphotericin B (AmB) encapsulated in Molecular Envelope Technology (MET) demonstrated significantly enhanced activity against Candida biofilms in vitro. This MET-AmB formulation shows promise for treating drug-refractory fungal infections, including ocular infections.
Area of Science:
- Mycology
- Nanotechnology
- Pharmacology
Background:
- Chronic Candida infections involve fungal cells embedded in biofilms, which are resistant to antifungal drugs.
- Candida biofilms are frequently associated with difficult-to-treat ocular fungal infections.
Purpose of the Study:
- To evaluate the efficacy of nanoparticulate amphotericin B (AmB) using Molecular Envelope Technology (MET) against Candida biofilms.
- To assess the stability of a MET-AmB ophthalmic formulation.
Main Methods:
- AmB was encapsulated into MET nanoparticles (N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan).
- The activity of MET-AmB against Candida albicans and Candida glabrata biofilms in vitro was determined.
- Confocal laser scanning microscopy (CLSM) was used to visualize nanoparticle penetration into biofilms.
- The stability of MET-AmB eye drops was evaluated at room temperature.
Main Results:
- MET-AmB exhibited significantly greater potency against C. albicans biofilms (EC50 ~30x lower) and C. glabrata biofilms (EC50 ~10x lower) compared to AmB alone.
- CLSM confirmed that MET nanoparticles penetrated the biofilm matrix and adhered to fungal cells.
- MET-AmB showed comparable activity to AmB alone against planktonic C. albicans cells.
- The MET-AmB eye drop formulation remained stable for at least 28 days at room temperature.
Conclusions:
- Nanoparticulate AmB delivered via MET demonstrates potent anti-biofilm activity against Candida species.
- These findings suggest that MET-loaded nanoparticles could be a viable strategy for treating challenging Candida biofilm infections, particularly in ocular settings.
