ABSTRACT
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.
Subject(s)
Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/therapeutic use , Leishmania/drug effects , Nanocomposites/therapeutic use , Animals , Cells, Cultured , In Vitro Techniques , Leishmania/physiology , Leishmania/ultrastructure , Macrophages/parasitology , Meglumine Antimoniate/chemistry , Meglumine Antimoniate/pharmacology , Meglumine Antimoniate/therapeutic use , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Mice , Mice, Inbred BALB C , Povidone/chemistry , Povidone/pharmacology , Povidone/therapeutic use , Silver/chemistry , Silver/pharmacology , Silver/therapeutic useABSTRACT
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.
