DOI QR코드

DOI QR Code

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

  • Parizi, Maryam Hakimi (Leishmaniasis Research Center, Kerman University of Medical Sciences) ;
  • Farajzadeh, Saeedeh (Department of Pediatric dermatology, Kerman University of Medical Sciences) ;
  • Sharifi, Iraj (Leishmaniasis Research Center, Kerman University of Medical Sciences) ;
  • Pardakhty, Abbas (Pharmaceutics Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences) ;
  • Parizi, Mohammad Hossein Daie (Department of Pediatrics, Kerman University of Medical Sciences) ;
  • Sharifi, Hamid (HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences) ;
  • Salarkia, Ehsan (Leishmaniasis Research Center, Kerman University of Medical Sciences) ;
  • Hassanzadeh, Saeid (Department of Pathobiology, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman)
  • Received : 2019.01.07
  • Accepted : 2019.03.13
  • Published : 2019.08.31

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 ($P{\leq}0.05$). 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 $200{\mu}g/ml$). 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.

Keywords

References

  1. Cortez de Sa J, Almeida-Souza F, Mondego-Oliveira R, Oliveira Idos S, Lamarck L, Magalhaes Ide F, Ataides-Lima AF, Ferreira Hda S, Abreu-Silva AL. Leishmanicidal, cytotoxicity and wound healing potential of Arrabidaea chica Verlot. BMC Complement Altern Med 2016; 16: 1.
  2. de Vries HJ, Reedijk SH, Schallig HD. Cutaneous leishmaniasis: recent developments in diagnosis and management. Am J Clin Dermatol 2015; 16: 99-109. https://doi.org/10.1007/s40257-015-0114-z
  3. Plano D, Baquedano Y, Moreno-Mateos D, Font M, Jimenez-Ruiz A, Palop JA, Sanmartin C. Selenocyanates and diselenides: a new class of potent antileishmanial agents. Eur J Med Chem 2011; 46: 3315-3323. https://doi.org/10.1016/j.ejmech.2011.04.054
  4. Sharifi F, Sharifi I, Zarean M, Parizi MH, Aflatoonian M, Harandi MF, Zahmatkesh R, Mashayekhi M, Kermanizadeh A. Spatial distribution and molecular identification of Leishmania species from endemic foci of south-eastern Iran. Iran J Parasitol 2012; 7: 45-52.
  5. Kazi KM, Mandal AS, Biswas N, Guha A, Chatterjee S, Behera M,Kuotsu K. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res 2010; 1: 374-380. https://doi.org/10.4103/0110-5558.76435
  6. Daie Parizi MH, Karvar M, Sharifi I, Bahrampour A, Heshmat Khah A, Rahnama Z,Baziar Z, Amiri R. The topical treatment of anthroponotic cutaneous leishmaniasis with the tincture of thioxolone plus benzoxonium chloride (Thio-Ben) along with cryotherapy: A single-blind randomized clinical trial. Dermatol Ther 2015; 28: 140-146. https://doi.org/10.1111/dth.12229
  7. Kim JE, Kim HS, Shin YJ, Lee CS, Won CH, Lee SA, Lee JW, Kim YS, Kang JS, Ye SK, Chung MH. LYR71, a derivative of trimeric resveratrol, inhibits tumorigenesis by blocking STAT3-mediated matrix metalloproteinase 9 expression. Exp Mol Med 2008; 40: 514-522. https://doi.org/10.3858/emm.2008.40.5.514
  8. Kim BH, Roh E, Lee HY, Lee IJ, Ahn B, Jung SH, Lee H, Han SB, Kim Y. Benzoxathiole derivative blocks lipopolysaccharide-induced nuclear factor-kappaB activation and nuclear factor-kappaB-regulated gene transcription through inactivating inhibitory kappaB kinase beta. Mol Pharmacol 2008; 73: 1309-1318. https://doi.org/10.1124/mol.107.041251
  9. Kim BH, Min YS, Choi JS, Baeg GH, Kim Y, Shin JW, Kim TY, Ye SK. Benzoxathiol derivative BOT-4-one suppresses L540 lymphoma cell survival and proliferation via inhibition of JAK3/STAT3 signaling. Exp Mol Med 2011; 43: 313-321. https://doi.org/10.3858/emm.2011.43.5.035
  10. Pardakhty A, Shakibaie M, Daneshvar H, Khamesipour A, Mohammadi-Khorsand T, Forootanfar H. Preparation and evaluation of niosomes containing autoclaved Leishmania major: a preliminary study. J Microencapsul 2012; 29: 219-224. https://doi.org/10.3109/02652048.2011.642016
  11. Attia IA, El-Gizawy SA, Fouda MA, Donia AM. Influence of a niosomal formulation on the oral bioavailability of acyclovir in rabbits. AAPS Pharm Sci Tech 2007; 8: 206-212. https://doi.org/10.1208/pt0804106
  12. Shahiwala A, Misra A. Studies in topical application of niosomally entrapped Nimesulide. J Pharm Pharm Sci 2002; 5: 220-225.
  13. Chandra D, Naik S. Leishmania donovani infection down-regulates TLR2-stimulated IL-12p40 and activates IL-10 in cells of macrophage/monocytic lineage by modulating MAPK pathways through a contact-dependent mechanism. Clin Exp Immunol 2008; 154: 224-234. https://doi.org/10.1111/j.1365-2249.2008.03741.x
  14. Satheesh Kumar S, Gokulasuriyan RK, Ghosh M. Comparative in-silico genome analysis of Leishmania (Leishmania) donovani: a step towards its species specificity. Meta Gene 2014; 2: 782-798. https://doi.org/10.1016/j.mgene.2014.10.003
  15. Yasinzai M, Khan M, Nadhman A, Shahnaz G. Drug resistance in leishmaniasis: current drug-delivery systems and future perspectives. Future Med Chem 2013; 5: 1877-1888. https://doi.org/10.4155/fmc.13.143
  16. Rahimpour Y, Hamishehkar H. Niosomes as carrier in dermal drug delivery. Recent Advances in Novel Drug Carrier Systems 2012; 1: 141-164.
  17. Yasam VR, Jakki SL, Natarajan J, Kuppusamy G. A review on novel vesicular drug delivery: proniosomes. Drug Deliv 2014; 21: 243-249. https://doi.org/10.3109/10717544.2013.841783
  18. Barcinski MA, DosReis GA. Apoptosis in parasites and parasite-induced apoptosis in the host immune system: a new approach to parasitic diseases. Braz J Med Biol Res 1999; 32: 395-401. https://doi.org/10.1590/S0100-879X1999000400003
  19. Paris C, Loiseau PM, Bories C, Breard J. Miltefosine induces apoptosis-like death in Leishmania donovani promastigotes. Antimicrob Agents Chemother 2004; 48: 852-859. https://doi.org/10.1128/AAC.48.3.852-859.2004
  20. Das R, Roy A, Dutta N, Majumder HK. Reactive oxygen species and imbalance of calcium homeostasis contributes to curcumin induced programmed cell death in Leishmania donovani. Apoptosis 2008; 13: 867-882. https://doi.org/10.1007/s10495-008-0224-7
  21. Nguewa PA, Fuertes MA, Cepeda V, Iborra S, Carrion J, Valladares B, Alonso C, Perez JM. Pentamidine is an antiparasitic and apoptotic drug that selectively modifies ubiquitin. Chem Biodivers 2005; 2: 1387-1400. https://doi.org/10.1002/cbdv.200590111
  22. Das M, Mukherjee SB, Shaha C. Hydrogen peroxide induces apoptosis-like death in Leishmania donovani promastigotes. J Cell Sci 2001; 114: 2461-2469. https://doi.org/10.1242/jcs.114.13.2461
  23. Weingartner A, Kemmer G, Muller FD, Zampieri RA, Gonzaga dos Santos M, Schiller J, Pomorski TG. Leishmania promastigotes lack phosphatidylserine but bind annexin V upon permeabilization or miltefosine treatment. PLoS One 2012; 7: e42070. https://doi.org/10.1371/journal.pone.0042070
  24. Basmaciyan L, Azas N, Casanova M. Calcein+/PI- as an early apoptotic feature in Leishmania. PLoS One 2017; 12: e0187756. https://doi.org/10.1371/journal.pone.0187756
  25. Hingorani R, Deng J, Elia J, Mcintyre C, Mittar D. Detection of Apoptosis Using the BD Annexin V FITC Assay on the BD FACSVerseTM System. San Jose, USA. BD Biosciences 2011, pp 1-12.
  26. Mera-Ramirez A, Castillo A, Orobio Y, Gomez MA, Gallego-Marin C. Screening of $TNF{\alpha}$, IL-10 and TLR4 single nucleotide polymorphisms in individuals with asymptomatic and chronic cutaneous leishmaniasis in Colombia: a pilot study. BMC Infect Dis 2017; 17: 177. https://doi.org/10.1186/s12879-017-2281-4
  27. Martorelli D, Muraro E, Merlo A, Turrini R, Fae DA, Rosato A, Dolcetti R. Exploiting the interplay between innate and adaptive immunity to improve immunotherapeutic strategies for Epstein-Barr-virus-driven disorders. Clin Dev Immunol 2012; 3: 931952.
  28. Bogdan C, Vodovotz Y, Nathan C. Macrophage deactivation by interleukln 10. J Exp Med 1991; 174: 3-7.
  29. Ambit A, Fasel N, Coombs GH, Mottram JC. An essential role for the Leishmania major metacaspase in cell cycle progression. Cell Death Differ 2008; 15: 113-122. https://doi.org/10.1038/sj.cdd.4402232
  30. Gonzalez IJ, Desponds C, Schaff C, Mottram JC, Fasel N. Leishmania major metacaspase can replace yeast metacaspase in programmed cell death and has arginine-specific cysteine peptidase activity. Int J Parasitol 2007; 37: 161-172. https://doi.org/10.1016/j.ijpara.2006.10.004
  31. Lee N, Gannavaram S, Selvapandiyan A, Debrabant A. Characterization of metacaspases with trypsin-like activity and their putative role in programmed cell death in the protozoan parasite Leishmania. Eukaryot Cell 2007; 6: 1745-1757. https://doi.org/10.1128/EC.00123-07
  32. Debrabant A, Lee N, Bertholet S, Duncan R, Nakhasi HL. Programmed cell death in trypanosomatids and other unicellular organisms. Int J Parasitol 2003; 33: 257-267. https://doi.org/10.1016/S0020-7519(03)00008-0

Cited by

  1. The assessment of apoptosis, toxicity effects and anti-leishmanial study of Chitosan/CdO core-shell nanoparticles, eco-friendly synthesis and evaluation vol.14, pp.4, 2019, https://doi.org/10.1016/j.arabjc.2021.103085
  2. Leishmanicidal potentials of Gossypium hirsutum extract and its fractions on Leishmania major in a murine model: parasite burden, gene expression, and histopathological profile vol.70, pp.6, 2019, https://doi.org/10.1099/jmm.0.001333