Amphotericin B Polymer Nanoparticles Show Efficacy against Species Biofilms.

Purpose: Chronic infections of are characterised by the embedding of budding and entwined filamentous fungal cells into biofilms. The biofilms are refractory to many drugs and biofilms are associated with ocular fungal infections. The objective was to test the activity of nanoparticulate amphotericin B (AmB) against 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 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 biofilms in vitro with the EC50 being ~30 times lower than AmB alone (EC50 MET-AmB = 1.176 μg mL, EC50 AmB alone = 29.09 μg mL). A similar superior activity was found for biofilms, where the EC50 was ~10× lower than AmB alone (EC50 MET-AmB = 0.0253 μg mL, EC50 AmB alone = 0.289 μg mL). CLSM imaging revealed that MET nanoparticles penetrated through the biofilm matrix and bound to fungal cells. The activity of MET-AmB was no different from the activity of AmB alone against cells in suspension (MET-AmB MIC90 = 0.125 μg mL, AmB alone MIC90 = 0.250 μg mL). 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 biofilm infections, such as refractory ocular fungal infections.