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

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. Sb(5+) 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 Sb(2)O(5)·nH(2)O nanoparticles (NPs), instead of molecular drugs. METHODOLOGY/PRINCIPAL FINDINGS: Sb(2)O(5)·nH(2)O NPs were synthesized by controlled SbCl(5) hydrolysis in a great excess of water. Sb(2)O(5)·nH(2)O 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 Sb(5+) 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: Sb(2)O(5)·nH(2)O 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, Sb(2)O(5)·nH(2)O hydrosols provide an opportunity to avoid toxic antimony (V) spreading throughout the body.