AgNP-PVP-meglumine antimoniate nanocomposite reduces Leishmania amazonensis infection in macrophages.

BACKGROUND: Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and presents different clinical manifestations. The adverse effects, immunosuppression and resistant strains associated with this disease necessitate the development of new drugs. Nanoparticles have shown potential as alternative antileishmanial drugs. We showed in a previous study the biosynthesis, characterization and ideal concentration of a nanocomposite that promoted leishmanicidal activity. In the present study, we conducted a specific analysis to show the mechanism of action of AgNP-PVP-MA (silver nanoparticle-polyvinylpyrrolidone-[meglumine antimoniate (Glucantime®)]) nanocomposite during Leishmania amazonensis infection in vitro. RESULTS: Through ultrastructural analysis, we observed significant alterations, such as the presence of small vesicles in the flagellar pocket and in the extracellular membrane, myelin-like structure formation in the Golgi complex and mitochondria, flagellum and plasma membrane rupture, and electrodense material deposition at the edges of the parasite nucleus in both evolutive forms. Furthermore, the Leishmania parasite infection index in macrophages decreased significantly after treatment, and nitric oxide and reactive oxygen species production levels were determined. Additionally, inflammatory, and pro-inflammatory cytokine and chemokine production levels were evaluated. The IL-4, TNF-α and MIP-1α levels increased significantly, while the IL-17 A level decreased significantly after treatment. CONCLUSIONS: Thus, we demonstrate in this study that the AgNP-PVP-MA nanocomposite has leishmanial potential, and the mechanism of action was demonstrated for the first time, showing that this bioproduct seems to be a potential alternative treatment for leishmaniasis.

A Novel Niosomal Combination of Selenium Coupled with Glucantime against Leishmania tropica.

There is no effective treatment modality available against different forms of leishmaniasis. Therefore, the aim of this study was to improve the penetration and efficacy of selenium and glucantime coupled with niosomes and compared them with their simple forms alone on in vitro susceptibility assays. In this study, the niosomal formulations of selenium and in combination with glucantime were prepared. The size and morphology of the niosomal formulations were characterized and the effectivity of the new formulation was also evaluated using in vitro MTT assay, intra-macrophage model, and gene expression profile. From the results obtained, no cytotoxicity effect was observed for niosomal and simple forms of drugs, as alone or in combination. Niosomal formulations of the drugs significantly showed more inhibitory effects (P ≤ 0.001) than the simple drugs when the selectivity index was considered. The gene expression levels of Interleukin (IL-10) significantly decreased, while the level of IL-12 and metacaspase significantly increased (P ≤ 0.001). The results of the present study showed that selenium plus glucantime niosome possess a potent anti-leishmanial effect and enhanced their lethal activity as evidenced by the in vitro experiments.

Biosynthesis, characterization and leishmanicidal activity of a biocomposite containing AgNPs-PVP-glucantime.

AIM: Development of functionalized nanocomposites containing AgNPs-PVP-Glucantime® to evaluate their leishmanicidal activity as a novel method for improving the pharmacological properties of the drug Glucantime® against extracellular promastigotes and intracellular amastigotes of Leishmania amazonensis in vitro to treat cutaneous leishmaniasis. MATERIALS & METHODS: The silver nanoparticles and nanocomposites prepared containing silver nanoparticles, polyvinylpyrrolidone and different amounts of Glucantime were characterized using transmission electron microscopy, x-ray diffraction, energy-dispersive x-ray spectroscopy and ζ potential analysis; in addition, the in vitro cytotoxicity was evaluated. RESULTS: The nanocomposites showed an inhibitory effect on the cellular viability of promastigote forms, with values of 47.06, 51.71 and 65.67% for nanocomposite1, nanocomposite2 and nanocomposite3, respectively, as well as a dose-dependent decrease in the infectivity index, with values of 33.33 and 23% for nanocomposite2 and nanocomposite3, respectively. CONCLUSION: The proposed nanocomposite reveals leishmanial activity and the absence of cytotoxicity in macrophages. Further investigations will be conducted in vivo.