Title:Silver Nanoparticles with High Loading Capacity of Amphotericin B: Characterization, Bactericidal and Antifungal Effects
VOLUME: 15 ISSUE: 6
Author(s):Victoria Leonhard, Roxana V. Alasino, Adrian Munoz and Dante M. Beltramo*
Affiliation:Centro de Excelencia en Productos y Procesos de Cordoba, Ceprocor, Centro de Excelencia en Productos y Procesos de Cordoba, Ceprocor, Centro de Excelencia en Productos y Procesos de Cordoba, Ceprocor, Centro de Excelencia en Productos y Procesos de Cordoba, Ceprocor
Keywords:Silver Nanoparticles, Amphotericin B, bactericidal effect, antifungal effect, plasma lipoproteins, cytotoxic.
Abstract:The purpose of this study was to evaluate the most appropriate conditions to generate silver
nanoparticles (AgNPs) loaded with a potent antimycotic drug like amphotericin B (AmB), characterize
the physicochemical properties, and to evaluate the cytotoxic effect and biological activity of these new
nanostructures as a potential nanocarrier for hydrophobic drugs. It was determined that the optimal molar
ratio between Ag and AmB is 1/1 given the uniformity of size around 170 nm of the nanoparticles
generated as well as their strongly negative ζ potential of -35 mV, a condition that favors repulsions
between AgNPs and inhibiting their aggregation. In this condition, only 0.8 mg.mL-1 of Ag is needed to
solubilize 5 mg.mL-1 of AmB, a concentration currently used in commercial formulations. It is important
to emphasize that the loading capacity (w/w) of this nanostructure is much higher than that of micellar
and liposomal formulations.
These AgNP-AmB nanoparticles retain both the bactericidal effect of silver and the cytotoxic and antifungal
effect of AmB. However, it was shown that these nanoparticles are spontaneously associated
with plasma lipoproteins (LDL and HDL), inhibiting their cytotoxic effects on red blood cells and on at
least two cell lines, Vero and H1299 and slightly reducing its bactericidal effect on P. aeruginosa. In
contrast, the antifungal effect of the formulation is maintained and is even higher than that when the
nanoparticle is not associated with lipoproteins, indicating that this association is of the reversible type.
The characterization of these nanoparticles is discussed as a potential new model formulation able to
improve the antifungal therapeutic efficiency of AmB.