In this study, we carried out extensive in vitro studies on various concentrations of tioxolone along with benzoxonium chloride and their niosomal forms against Leishmania tropica. Niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. This study measured leishmanicidal activity against promastigote and amastigote, apoptosis and gene expression levels of free solution and niosomal-encapsulated tioxolone along with benzoxonium chloride. Span/Tween 60 niosome had good physical stability and high encapsulation efficiency (more than 97%). The release profile of the entrapped compound showed that a gradual release rate. The combination of niosomal forms on promastigote and amastigote were more effective than glucantime. Also, the niosomal form of this compound was significantly less toxic than glucantime (P≤0.05). The flowcytometric analysis on niosomal form of drugs showed that higher number of early apoptotic event as the principal mode of action (89.13% in 200 μg/ml). Also, the niosomal compound increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 gene, which further confirming the immunomodulatory role as the mechanism of action. We observed the synergistic effects of these 2 drugs that induced the apoptotic pathways and also up regulation of an immunomodulatory role against as the main mode of action. Also, niosomal form of this combination was safe and demonstrated strong anti-leishmaniasis effects highlights further therapeutic approaches against anthroponotic cutaneous leishmaniasis in future planning.
Apoptosis ; Gene Expression ; In Vitro Techniques ; Interleukin-10 ; Interleukin-12 ; Leishmania tropica ; Leishmania ; Leishmaniasis, Cutaneous ; Liposomes ; Methods ; Up-Regulation

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.
Gene Expression ; In Vitro Techniques ; Interleukin-12 ; Interleukins ; Leishmania tropica ; Leishmania ; Leishmaniasis ; Liposomes ; Selenium ; Transcriptome

Objective: To investigate the repellent effect of neem, juniper and eucalyptus extracts as a form of protection against Paederus beetles, which are a cause of linear dermatitis in Iran. Methods: After collecting and extracting plant samples, the extracts were tested on Paederus beetles in three concentrations (2.5%, 5.0% and 10.0%) with direct method under laboratory conditions. The data were analyzed using SPSS software (version 20). Results: The results indicated that there was a significant difference between neem with juniper and eucalyptus at the 2.5% and 5.0% concentrations (P < 0.05), whereas there was a significant difference between all three extracts at the 10.0% concentration (P < 0.05). Conclusions: This is the first report on the repellent effect of these three plant extracts on Paederus beetles. Neem oil appeared to have the largest effect on Paederus spp. and juniper essential oil exhibited the second highest repellency, followed by eucalyptus.

Objective: To explore the antileishmanial effect of tioxolone and its niosomal form against Leishmania tropica. Methods: Tioxolone niosomes were prepared by the hydration method and were evaluated for morphology, size, release study, and encapsulation efficiency. The cytotoxicity of tioxolone and its niosomal form was measured by MTT assay, leishmanicidal activity against promastigote and amastigote by MTT assay, apoptosis by flow cytometry, IL-12, IL-10 and metacaspase gene expression levels by q-PCR. Results: Span/Tween 40 and Span/Tween 60 niosomes had good physical stability as depicted in their size distribution curves and high encapsulation efficiency (>99%). The release profile of the entrapped compounds showed Fickian's model of tioxolone delivery based on diffusion through lipid bilayers. With the IC