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Tioxolone niosomes exert antileishmanial effects on Leishmania tropica by promoting promastigote apoptosis and immunomodulation
Authors: 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
Number of views: 214
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 gene.
Conclusions: 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.