Korean J Parasitol.  2019 Aug;57(4):359-368. 10.3347/kjp.2019.57.4.359.

Antileishmanial Activity of Niosomal Combination Forms of Tioxolone along with Benzoxonium Chloride against Leishmania tropica

Affiliations
  • 1Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
  • 2Department of Pediatric dermatology, Kerman University of Medical Sciences, Kerman, Iran. s.farajzadeh97@gmail.com
  • 3Pharmaceutics Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
  • 4Department of Pediatrics, Kerman University of Medical Sciences, Kerman, Iran.
  • 5HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran.
  • 6Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.

Abstract

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.

Keyword

Leishmania tropica; tioxolone; benzoxonium chloride; niosome

MeSH Terms

Apoptosis
Gene Expression
In Vitro Techniques
Interleukin-10
Interleukin-12
Leishmania tropica*
Leishmania*
Leishmaniasis, Cutaneous
Liposomes
Methods
Up-Regulation
Interleukin-10
Interleukin-12
Liposomes
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