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

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 

作者机构：Leishmaniasis Research CenterKerman University of Medical SciencesKermanIran Department of Pediatric dermatologyKerman University of Medical SciencesKermanIran Pharmaceutics Research CenterNeuropharmacology InstituteKerman University of Medical SciencesKermanIran Department of PediatricsKerman University of Medical SciencesKermanIran HIV/STI Surveillance Research Centerand WHO Collaborating Center for HIV SurveillanceInstitute for Futures Studies in HealthKerman University of Medical SciencesKermanIran Research Center of Tropical and Infectious DiseasesKerman University of Medical SciencesKermanIran 

出 版 物：《Asian Pacific Journal of Tropical Medicine》 (亚太热带医药杂志（英文版）)

年 卷 期：2019年第12卷第8期

页      面：365-374页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：financially supported by the Iran National Science Foundation under Grant ID 95839151 to Saeedeh Farajzadeh 

主　　题：Niosome Tioxolone Leishmania tropica Apoptosis 

摘      要：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.