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Purpose: Chronic infections of <i>Candida albicans</i> are characterised by the embedding of budding and entwined filamentous fungal cells into biofilms. The biofilms are refractory to many drugs and <i>Candida</i> biofilms are associated with ocular fungal infections. The objective was to test the activity of nanoparticulate amphotericin B (AmB) against <i>Candida</i> 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 <i>Candida</i> 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 <i>C. albicans</i> 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 <i>Candida glabrata</i> 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 <i>C. albicans</i> biofilm matrix and bound to fungal cells. The activity of MET-AmB was no different from the activity of AmB alone against <i>C. albicans</i> 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 <i>Candida</i> biofilm infections, such as refractory ocular fungal infections.