Amphotericin B-silver hybrid nanoparticles: synthesis, properties and antifungal activity.

High antifungal activity is reported, in comparison with commercially available products, of a novel hybrid system based on silver nanoparticles synthesized using a popular antifungal macrocyclic polyene amphotericin B (AmB) acting both as a reducing and stabilizing/capping agent. The synthesis reaction proceeds in an alkaline environment which prevents aggregation of AmB itself and promotes nanoparticle formation. The innovative approach produces monodisperse (PDI=0.05), AmB-coated silver nanoparticles (AmB-AgNPs) with the diameter ~7nm. The products were characterized using imaging (electron microscopy) and spectroscopic (UV-vis and infrared absorption, dynamic light scattering and Raman scattering) methods. The nanoparticles were tested against Candida albicans, Aspergillus niger and Fusarium culmorum species. For cytotoxicity studies CCD-841CoTr and THP-1 cell lines were used. Particularly high antifungal activity of AmB-AgNPs is interpreted as the result of synergy between the antifungal activity of amphotericin B and silver antimicrobial properties (Ag(+) ions release). FROM THE CLINICAL EDITOR: Amphotericin B (AmB) is a common agent used for the treatment against severe fungal infections. In this article, the authors described a new approach in using a combination of AmB and silver nanoparticles, in which the silver nanoparticles were synthesized and stabilized by AmB. Experimental data confirmed synergistic antifungal effects between amphotericin B and silver. This novel synthesis process could potentially be important in future drug development and fabrication.

The orientation of the transition dipole moments of a polyene antibiotic Amphotericin B under UV-VIS studies.

Amphotericin B (AmB) belongs to naturally occurring fluorescent antibiotics, commonly used in the treatment of life-threatening fungal infections. Open question regarding mechanism of action of this molecule calls for its orientation and organization studies in biomembranes. Here, we present studies on linear dichroism and fluorescence polarization of AmB embedded in isotropic and oriented poly(vinyl) alcohol films to characterize their transition dipole moments to low energy excited electronic transitions S1 (2 Ag(-)) and S2 (1 Bu(+)). The dichroic ratio and fluorescence anisotropy data were analyzed for stretched PVA films doped AmB. The results show that the transition moment for absorption makes an angle φ = 27° ± 2° with the molecular axis of AmB defined by the film stretching direction. The angles between the absorption and emission transition moments have been found for both the low excited electronic states, S2 (ß = 4° ± 5°) and S1 (ß = 6° ± 5°). The fluorescence anisotropy analysis from the S2 state reveals additional component assigned to antiparallel AmB dimeric structure.

Self-association of amphotericin B: spontaneous formation of molecular structures responsible for the toxic side effects of the antibiotic.

Amphotericin B (AmB) is a lifesaving antibiotic used to treat deep-seated mycotic infections. Both the pharmaceutical activity and highly toxic side effects of the drug rely on its interaction with biomembranes, which is governed by the molecular organization of AmB. In the present work, we present a detailed analysis of self-assembly of AmB molecules in different environments, interesting from the physiological standpoint, based on molecular spectroscopy techniques: electronic absorption, circular dichroism, steady state and time-resolved fluorescence and molecular dynamic calculations. The results show that, in the water medium, AmB self-associates to dimeric structures, referred to as "parallel" and "antiparallel". AmB dimers can further assemble into tetramers which can play a role of transmembrane ion channels, affecting electrophysiological homeostasis of a living cell. Understanding structural determinants of self-assembly of AmB opens a way to engineering preparations of the drug which retain pharmaceutical effectiveness under reduced toxicity.