Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs

Antonia MR Franco,1 Iryna Grafova,2 Fabiane V Soares,1,3 Gennaro Gentile,4 Claudia DC Wyrepkowski,1,3 Marcos A Bolson,5 Ézio Sargentini Jr,5 Cosimo Carfagna,4 Markku Leskelä,2 Andriy Grafov2 1Laboratory of Leishmaniasis and Chagas Disease, National Institute of Amazonian Researc...

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Autores principales:	Franco AMR, Grafova I, Soares FV, Gentile G, Wyrepkowski CDC, Bolson MA, Sargentini Jr E, Carfagna C, Leskelä M, Grafov A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	nanoparticle leishmaniasis hydrated antimony (V) oxide TEM microscopy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/02e4d814a6c5482a86cd7d94b21ae529
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spelling	oai:doaj.org-article:02e4d814a6c5482a86cd7d94b21ae5292021-12-02T01:19:26ZNanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs1178-2013https://doaj.org/article/02e4d814a6c5482a86cd7d94b21ae5292016-12-01T00:00:00Zhttps://www.dovepress.com/nanoscaled-hydrated-antimony-v-oxide-as-new-approach-to-the-first-line-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Antonia MR Franco,1 Iryna Grafova,2 Fabiane V Soares,1,3 Gennaro Gentile,4 Claudia DC Wyrepkowski,1,3 Marcos A Bolson,5 Ézio Sargentini Jr,5 Cosimo Carfagna,4 Markku Leskelä,2 Andriy Grafov2 1Laboratory of Leishmaniasis and Chagas Disease, National Institute of Amazonian Research (INPA), Manaus, Amazonas, Brazil; 2Department of Chemistry, University of Helsinki, Helsinki, Finland; 3Multi-Institutional Post-Graduate Program in Biotechnology, Federal University of Amazonas, Manaus, Amazonas, Brazil; 4Institute for Polymers, Composites, and Biomaterials, National Research Council, Pozzuoli, Naples Province, Italy; 5Laboratory of Environmental Chemistry, National Institute of Amazonian Research (INPA), Manaus, Amazonas, Brazil Background: Coordination compounds of pentavalent antimony have been, and remain, the first-line drugs in leishmaniasis treatment for >70 years. Molecular forms of Sb (V) complexes are commercialized as sodium stibogluconate (Pentostam®) and meglumine antimoniate (MA) (Glucantime®). Ever-increasing drug resistance in the parasites limits the use of antimonials, due to the low drug concentrations being administered against high parasitic counts. Sb5+ toxicity provokes severe side effects during treatment. To enhance therapeutic potency and to increase Sb (V) concentration within the target cells, we decided to try a new active substance form, a hydrosol of Sb2O5⋅nH2O nanoparticles (NPs), instead of molecular drugs. Methodology/principal findings: Sb2O5⋅nH2O NPs were synthesized by controlled SbCl5 hydrolysis in a great excess of water. Sb2O5⋅nH2O phase formation was confirmed by X-ray diffraction. The surface of Sb (V) NPs was treated with ligands with a high affinity for target cell membrane receptors. The mean particle size determined by dynamic light scattering and transmission electron microscopy was ~35–45 nm. In vitro tests demonstrated a 2.5–3 times higher antiparasitic activity of Sb (V) nanohybrid hydrosols, when compared to MA solution. A similar comparison for in vivo treatment of experimental cutaneous leishmaniasis with Sb5+ nanohybrids showed a 1.75–1.85 times more effective decrease in the lesions. Microimages of tissue fragments confirmed the presence of NPs inside the cytoplasm of infected macrophages. Conclusion/significance: Sb2O5⋅nH2O hydrosols are proposed as a new form of treatment for cutaneous leishmaniasis caused by Leishmania amazonensis. The NPs penetrate directly into the affected cells, creating a high local concentration of the drug, a precondition to overcoming the parasite resistance to molecular forms of pentavalent antimonials. The nanohybrids are more effective at a lower dose, when compared to MA, the molecular drug. Our data suggest that the new form of treatment has the potential to reduce and simplify the course of cutaneous leishmaniasis treatment. At the same time, Sb2O5⋅nH2O hydrosols provide an opportunity to avoid toxic antimony (V) spreading throughout the body. Keywords: nanoparticle, leishmaniasis, hydrated antimony (V) oxide, TEM, transmission electron microscopyFranco AMRGrafova ISoares FVGentile GWyrepkowski CDCBolson MASargentini Jr ECarfagna CLeskelä MGrafov ADove Medical Pressarticlenanoparticleleishmaniasishydrated antimony (V) oxideTEM microscopyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6771-6780 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	nanoparticle leishmaniasis hydrated antimony (V) oxide TEM microscopy Medicine (General) R5-920
spellingShingle	nanoparticle leishmaniasis hydrated antimony (V) oxide TEM microscopy Medicine (General) R5-920 Franco AMR Grafova I Soares FV Gentile G Wyrepkowski CDC Bolson MA Sargentini Jr E Carfagna C Leskelä M Grafov A Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs
description	Antonia MR Franco,1 Iryna Grafova,2 Fabiane V Soares,1,3 Gennaro Gentile,4 Claudia DC Wyrepkowski,1,3 Marcos A Bolson,5 Ézio Sargentini Jr,5 Cosimo Carfagna,4 Markku Leskelä,2 Andriy Grafov2 1Laboratory of Leishmaniasis and Chagas Disease, National Institute of Amazonian Research (INPA), Manaus, Amazonas, Brazil; 2Department of Chemistry, University of Helsinki, Helsinki, Finland; 3Multi-Institutional Post-Graduate Program in Biotechnology, Federal University of Amazonas, Manaus, Amazonas, Brazil; 4Institute for Polymers, Composites, and Biomaterials, National Research Council, Pozzuoli, Naples Province, Italy; 5Laboratory of Environmental Chemistry, National Institute of Amazonian Research (INPA), Manaus, Amazonas, Brazil Background: Coordination compounds of pentavalent antimony have been, and remain, the first-line drugs in leishmaniasis treatment for >70 years. Molecular forms of Sb (V) complexes are commercialized as sodium stibogluconate (Pentostam®) and meglumine antimoniate (MA) (Glucantime®). Ever-increasing drug resistance in the parasites limits the use of antimonials, due to the low drug concentrations being administered against high parasitic counts. Sb5+ toxicity provokes severe side effects during treatment. To enhance therapeutic potency and to increase Sb (V) concentration within the target cells, we decided to try a new active substance form, a hydrosol of Sb2O5⋅nH2O nanoparticles (NPs), instead of molecular drugs. Methodology/principal findings: Sb2O5⋅nH2O NPs were synthesized by controlled SbCl5 hydrolysis in a great excess of water. Sb2O5⋅nH2O phase formation was confirmed by X-ray diffraction. The surface of Sb (V) NPs was treated with ligands with a high affinity for target cell membrane receptors. The mean particle size determined by dynamic light scattering and transmission electron microscopy was ~35–45 nm. In vitro tests demonstrated a 2.5–3 times higher antiparasitic activity of Sb (V) nanohybrid hydrosols, when compared to MA solution. A similar comparison for in vivo treatment of experimental cutaneous leishmaniasis with Sb5+ nanohybrids showed a 1.75–1.85 times more effective decrease in the lesions. Microimages of tissue fragments confirmed the presence of NPs inside the cytoplasm of infected macrophages. Conclusion/significance: Sb2O5⋅nH2O hydrosols are proposed as a new form of treatment for cutaneous leishmaniasis caused by Leishmania amazonensis. The NPs penetrate directly into the affected cells, creating a high local concentration of the drug, a precondition to overcoming the parasite resistance to molecular forms of pentavalent antimonials. The nanohybrids are more effective at a lower dose, when compared to MA, the molecular drug. Our data suggest that the new form of treatment has the potential to reduce and simplify the course of cutaneous leishmaniasis treatment. At the same time, Sb2O5⋅nH2O hydrosols provide an opportunity to avoid toxic antimony (V) spreading throughout the body. Keywords: nanoparticle, leishmaniasis, hydrated antimony (V) oxide, TEM, transmission electron microscopy
format	article
author	Franco AMR Grafova I Soares FV Gentile G Wyrepkowski CDC Bolson MA Sargentini Jr E Carfagna C Leskelä M Grafov A
author_facet	Franco AMR Grafova I Soares FV Gentile G Wyrepkowski CDC Bolson MA Sargentini Jr E Carfagna C Leskelä M Grafov A
author_sort	Franco AMR
title	Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs
title_short	Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs
title_full	Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs
title_fullStr	Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs
title_full_unstemmed	Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs
title_sort	nanoscaled hydrated antimony (v) oxide as a new approach to first-line antileishmanial drugs
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/02e4d814a6c5482a86cd7d94b21ae529
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Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs

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