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Tioxolone niosomes exert antileishmanial effects on Leishmania tropica by promoting promastigote apoptosis and immunomodulation

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Asian Pacific Journal of Tropical Medicine 2019年第8期12卷 365-374页

作者： Maryam Hakimi Parizi Iraj Sharifi saeedeh farajzadeh Abbas Pardakhty Mohammad Hossein Daie Parizi Hamid Sharifi Ali Reza Keyhani Mahshid Mostafavi Mehdi Bamorovat Ahmad Khosravi Daryoush Ghaffari Leishmaniasis Research Center Kerman University of Medical SciencesKermanIran Department of Pediatric dermatology Kerman University of Medical SciencesKermanIran Pharmaceutics Research Center Neuropharmacology InstituteKerman University of Medical SciencesKermanIran Department of Pediatrics Kerman University of Medical SciencesKermanIran HIV/STI Surveillance Research Center and WHO Collaborating Center for HIV SurveillanceInstitute for Futures Studies in HealthKerman University of Medical SciencesKermanIran Research Center of Tropical and Infectious Diseases Kerman University of Medical SciencesKermanIran

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 IC50 value for amastigote as(24.5±2.1) μg/mL and selectivity index as 10.5, the Span/Tween 60 niosome(NT2) had a superior effect to other drugs. The CC50 value and IC50 of promastigote value for NT2 were(257.5±24.5) μg/mL and(164.8±20.6) μg/mL, respectively. The flow cytometric analysis showed that tioxolone and niosomal forms induced apoptosis of Leishmania tropica promastigotes in a dose-dependent manner. NT2 increased the expression level of IL-12 and metacaspase genes and decreased the expression level of the IL-10 ***: Niosomes of tioxolone play an immunomodulatory role in increasing Th1 cytokine profile and inhibiting the Th2 cytokine profile. It could be used for treatment of anthroponotic cutaneous leishmaniasis.

关键词： Niosome Tioxolone Leishmania tropica Apoptosis

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