Abstract
BackgroundLeishmaniasis 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.ResultsThrough 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.ConclusionsThus, 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.
Highlights
Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and presents different clinical manifestations
Anti-amastigote activity promoted by the Silver Nanoparticles (AgNP)-PVP-Meglumine Antimoniate (MA) nanocomposite Following treatment with AgNP-PVP-MA nanocomposite in the concentration described or amphotericin B (0.5 μg/mL), as a reference drug, after 24 h of incubation, infection levels were reduced with both the reference drug (275 mean value of infection) and the nanocomposite (284.33 mean value of infection) compared to those in the untreated control group (Fig. 1A), with 576 mean value of infection, demonstrating the anti-leishmanial potential of the nanocomposite
A significant reduction in the amastigote number in the group treated with AgNP-PVP-MA nanocomposite (Fig. 1C – white arrow) compared to those in the untreated control group (Fig. 1B) and the amphotericin B-treated group (Fig. 1D – white arrow) was determined by fluorescence microscopy
Summary
Leishmaniasis is an infectious disease caused by parasites of the genus Leishmania and presents different clinical manifestations. In Brazil, American cutaneous leishmaniasis (ACL) caused by parasites of the genus Leishmania is transmitted by sandflies of the genus Lutzomyia [2], and the treatment comprises first-line drugs such as pentavalent antimonials, which, in Brazil, are represented by the antimoniate of N-methylglucamine or meglumine antimoniate [3]. Due to the resistance of some Leishmania species to the drugs mentioned above, suppressed immunity and different scenarios of adverse effects in patients when treated with them [5], the search for new treatment criteria and therapeutic alternatives with reduced side effects that improve the effectiveness of traditional methods are studied continuously [6]. It is noteworthy that the delivery of therapeutic compounds to specific targets has been one of the problems in the treatment of diseases and that the conventional administration of some drugs is characterized by limited efficacy, low distribution and poor target selectivity [6, 7]
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