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Title: Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs
Authors: Franco, A. M.
Grafova, Iryna A.
Soares, Fabiane Veloso
Gentile, Gennaro
Wyrepkowski, Claudia D C
Bolson, Marcos A.
Sargentini, Ézio
Carfagna, Cosimo
Leskelä, Markku A.
Grafov, Andrèi Andriy
Keywords: Antimony
Antimony Oxide Nanopmeglumine Antimonate
Nanopunclassified Drug
Antimony Oxide
Antiprotozoal Agent
Animals Experiment
Animals Model
Animals Tissue
Antiparasitic Activity
Controlled Study
Drug Activity
In Vitro Study
Particle Size
Skin Leishmaniasis
Syrian Hamster
Drug Effects
Leishmania Mexicana
Leishmaniasis, Cutaneous
Photon Correlation Spectroscopy
Preclinical Study
Transmission Electron Microscopy
X-ray Diffraction
Antiprotozoal Agents
Drug Evaluation, Preclinical
Dynamic Light Scattering
Leishmania Mexicana
Leishmaniasis, Cutaneous
Transmission Electron Microscopy
Particle Size
X-ray Diffraction
Issue Date: 2016
metadata.dc.publisher.journal: International Journal of Nanomedicine
metadata.dc.relation.ispartof: Volume 11, Pags. 6771-6780
Abstract: 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. © 2016 Franco et al.
metadata.dc.identifier.doi: 10.2147/IJN.S121096
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