Original Article
Magnetic nanoparticles as a drug delivery system that enhance fungicidal activity of polyene antibiotics

https://doi.org/10.1016/j.nano.2016.07.006Get rights and content

Abstract

This study was designed to assess the antifungal/anti-biofilm and hemolytic properties of two polyene antibiotics, amphotericin B (AMF) and nystatin (NYS), attached to the surface of magnetic nanoparticles (MNP) against clinical isolates of Candida species and human red blood cells, respectively. The developed nanosystems, MNP@AMF and MNP@NYS, displayed stronger fungicidal activity than unbound AMF or NYS. Synergistic activity was observed with a combination of polyenes and MNPs against all tested Candida strains. Nanosystems were more potent than unbound agents when tested against Candida strains in the presence of pus, and as agents able to prevent Candida biofilm formation. The observed inactivation of catalase Cat1 in Candida cells upon treatment with the nanosystems suggests that disruption of the oxidation–reduction balance is a mechanism leading to inhibition of Candida growth. The significant decrease of polyenes lytic activity against host cells after their attachment to MNPs surface indicates improvement in their biocompatibility.

Graphical Abstract

Overall properties and applications of synthesized magnetic nanoparticles coated by amphotericin B (red balls) or nystatin (blue balls) or their mixture against Candida cells.

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Section snippets

Synthesis of magnetic nanoparticles functionalized by polyene antibiotics

Magnetic nanoparticles were obtained using a well-known modification of the Massart methods which is based on the co-precipitation of iron chloride salts (FeCl2⋅4H2O and FeCl3⋅6H2O) under treatment by ammonium hydroxide (25%).32 Core–shell magnetic nanostructures with terminal propylo-amine groups were synthesized according to previously described modification of Stöber methods.33 Immobilization of polyene antibiotics onto the surface of nanoparticles was achieved by reaction between the

Nanoparticle characterization

The obtained magnetic nanoparticles were characterized by ATR FT-IR spectroscopy. Figure 1, A shows the ATR FT-IR spectra of bare magnetic nanoparticles (MNP), aminosilane coated magnetic nanoparticles (MNP@NH2), AMF and magnetic nanoparticles functionalized by AMF (MNP@AMF) as well as NYS and magnetic nanoparticles functionalized by nystatin MNP@NYS. In all samples the presence of a magnetic core is indicated by a band between 536 and 562 cm−1, which corresponds to the Fe–O stretching mode of

Discussion

The ability of nanoparticles to penetrate microorganisms cell membranes and biofilm networks opens a gate for the development of new methods to treat and prevent microbial infections. Recent data suggest that certain properties of metal nanoparticles, such as the induction of oxidative stress as well as membrane activity, are potentially useful qualities to develop new antifungal agents.46 The application of nanotechnology to provide new methods of fungal infection treatment involves silver,

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    This work was supported by the National Science Center, Poland under grants UMO-2012/07/B/NZ6/03504 (to R.B.) and UMO-2014/15/D/NZ6/02665 (to K.N.). In 2016 dr K. Niemirowicz was awarded by fellowship from Foundation for Polish Science (FNP). The equipment used for analysis in the Center of Synthesis and Analysis BioNanoTechno of University of Bialystok was funded by EU, as part of the Operational Program Development of Eastern Poland 2007-2013, project: POPW.01.03.00-20-034/09-00.

    The authors declare no competing interests.

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