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Título: | Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs |
Autor: | 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 |
Palavras-chave: | Antimony Antimony Oxide Nanopmeglumine Antimonate Nanopunclassified Drug Antimony Antimony Oxide Antiprotozoal Agent Nanopoxide Adult Animals Experiment Animals Model Animals Tissue Antiparasitic Activity Controlled Study Cytoplasm Drug Activity In Vitro Study Macrophage Male Nanotechnology Nonhuman Particle Size Skin Leishmaniasis Syrian Hamster Animals Chemistry Drug Effects Leishmania Mexicana Leishmaniasis, Cutaneous Mesocricetus Pathogenicity Photon Correlation Spectroscopy Preclinical Study Procedures Transmission Electron Microscopy X-ray Diffraction Animal Antimony Antiprotozoal Agents Drug Evaluation, Preclinical Dynamic Light Scattering Leishmania Mexicana Leishmaniasis, Cutaneous Male Mesocricetus Transmission Electron Microscopy Nanoparticles Oxides Particle Size X-ray Diffraction |
Data do documento: | 2016 |
Revista: | International Journal of Nanomedicine |
É parte de: | 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. |
DOI: | 10.2147/IJN.S121096 |
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