Advertisement

Leishmanicidal effects of amphotericin B in combination with selenium loaded on niosome against Leishmania tropica

  • Mahshid Mostafavi
  • Saeedeh FarajzadehEmail author
  • Iraj Sharifi
  • Payam Khazaeli
  • Hamid Sharifi
Original Article
  • 14 Downloads

Abstract

The strategy for improving the treatment of leishmaniasis by the World Health Organization, is the development of new drugs and combination therapy. The aim of this survey was to investigate the effect of amphotericin B (AmB) in combination with selenium, in a simple or niosomal form, on Leishmania tropica (L. tropica) by in vitro advanced assays. In this study, a niosomal formulation of AmB with selenium was prepared and characterized based on size and morphology. Using MTT assay, macrophage model, flow cytometry, and qPCR, the cytotoxicity and efficiency of the niosomal formulation and simple form of combination were evaluated. No toxicity was reported for both the niosomal and simple form of the combination. The niosomal formulation significantly showed higher inhibitory effect on the promastigote and amastigote forms of L. tropica than simple combination form. Interleukin (IL)-10 significantly decreased while the level of IL-12 and metacasoase as Th-1 activator significantly increased (P < 0.001). The findings of this study indicated that niosomes are the stable carriers for this combination, easy to produce and provide promising results as an effective formulation in the inhibition of extracellular and intracellular forms of L. tropica in compared with simple combination form.

Keywords

Amphotericin B Selenium Niosome Gene expression Leishmania tropica 

Notes

Acknowledgements

This project (Protocol no. 94/691) was reviewed and approved by the Leishmaniasis Research Center and received financial support from the Vice Chancellor of research at the Kerman University of Medical Sciences located in Kerman in Iran. This study is a part of a PhD dissertation for pursuit of a PhD by research degree in leishmaniasis and skin diseases.

Author Contributions

SF and MM conceived and designed the study. PK contributed to preparation of niosomal formulation. HS analyzed the data. IS and MM contributed to study concept, data interpretation and manuscript preparation. All authors contributed in reviewed, revised, and confirmed the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interests.

References

  1. Agrawal S, Rai M, Sundar S (2005) Management of visceral leishmaniasis: Indian perspective. J Postgrad Med 51(Suppl 1):S53–S57PubMedGoogle Scholar
  2. Aguiar MG, Pereira AMM et al (2010) Reductions in skin and systemic parasite burdens as a combined effect of topical paromomycin and oral miltefosine treatment of mice experimentally infected with Leishmania (Leishmania) amazonensis. Antimicrob Agents Chemother 54:4699–4704.  https://doi.org/10.1128/AAC.00809-10 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Alvar J, Vélez ID, Bern C et al (2012) Leishmaniasis worldwide and global estimates of its incidence. PLoS ONE 7:e35671.  https://doi.org/10.1371/journal.pone.0035671 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Ambit A, Fasel N, Coombs GH, Mottram JC (2008) An essential role for the Leishmania major metacaspase in cell cycle progression. Cell Death Differ 15:113–122.  https://doi.org/10.1038/sj.cdd.4402232 CrossRefPubMedGoogle Scholar
  5. Annaloro C, Olivares C, Usardi P et al (2009) Retrospective evaluation of amphotericin B deoxycholate toxicity in a single centre series of haematopoietic stem cell transplantation recipients. J Antimicrob Chemother 63:625–626.  https://doi.org/10.1093/jac/dkn549 CrossRefPubMedGoogle Scholar
  6. Bayindir ZS, Be AB, Yüksel N (2015) Paclitaxel-loaded niosomes for intravenous administration: pharmacokinetics and tissue distribution in rats. Turk J Med Sci 45:1403–1412CrossRefGoogle Scholar
  7. Beheshti N, Soflaei S, Shakibaie M et al (2013) Efficacy of biogenic selenium nanoparticles against Leishmania major: in vitro and in vivo studies. J Trace Elem Med Biol 27:203–207.  https://doi.org/10.1016/j.jtemb.2012.11.002 CrossRefPubMedGoogle Scholar
  8. Cassago A, Rodrigues EM, Prieto EL et al (2006) Identification of Leishmania selenoproteins and SECIS element. Mol Biochem Parasitol 149:128–134.  https://doi.org/10.1016/j.molbiopara.2006.05.002 CrossRefPubMedGoogle Scholar
  9. Chandra D, Naik S, Naik S (2008) 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.  https://doi.org/10.1111/j.1365-2249.2008.03741.x CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chattopadhyay A, Jafurulla M (2011) A novel mechanism for an old drug: amphotericin B in the treatment of visceral leishmaniasis. Biochem Biophys Res Commun 416:7–12.  https://doi.org/10.1016/j.bbrc.2011.11.023 CrossRefPubMedGoogle Scholar
  11. Croft SL, Seifert K, Yardley V (2006a) Current scenario of drug development for leishmaniasis. Indian J Med Res 123:399–410PubMedGoogle Scholar
  12. Croft SL, Sundar S, Fairlamb AH (2006b) Drug resistance in Leishmaniasis. Clin Microbiol Rev 19:111–126.  https://doi.org/10.1128/CMR.19.1.111-126.2006 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Cunha MA, de Cassia Soler R, Leão ACQ, Lindoso JAL (2015) Efficacy and safety of liposomal amphotericin B for the treatment of mucosal leishmaniasis from the new world: a retrospective study. Am J Trop Med Hyg 93:1214–1218.  https://doi.org/10.4269/ajtmh.15-0033 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Debrabant A, Lee N, Bertholet S et al (2003) Programmed cell death in trypanosomatids and other unicellular organisms. Int J Parasitol 33:257–267CrossRefGoogle Scholar
  15. Donowitz GR (1994) Tissue-directed antibiotics and intracellular parasites: complex interaction of phagocytes, pathogens, and drugs. Clin Infect Dis 19:926–930.  https://doi.org/10.1093/clinids/19.5.926 CrossRefPubMedGoogle Scholar
  16. Duarte MC, Tavares GSV, Valadares DG et al (2016) Antileishmanial activity and mechanism of action from a purified fraction of Zingiber officinalis Roscoe against Leishmania amazonensis. Exp Parasitol 166:21–28.  https://doi.org/10.1016/j.exppara.2016.03.026 CrossRefPubMedGoogle Scholar
  17. Escudero-Martínez JM, Pérez-Pertejo Y, Reguera RM et al (2017) Antileishmanial activity and tubulin polymerization inhibition of podophyllotoxin derivatives on Leishmania infantum. Int J Parasitol Drugs Drug Resist 7:272–285.  https://doi.org/10.1016/J.IJPDDR.2017.06.003 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Farajzadeh S, Esfandiarpour I, Haghdoost AA et al (2015a) Comparison between combination therapy of oral terbinafine and cryotherapy versus systemic meglumine antimoniate and cryotherapy in cutaneous leishmaniasis: a randomized clinical trial. Iran J Parasitol 10:1–8PubMedPubMedCentralGoogle Scholar
  19. Farajzadeh S, Heshmatkhah A, Vares B et al (2015b) Topical terbinafine in the treatment of cutaneous leishmaniasis: triple blind randomized clinical trial. J Parasit Dis. 1:1.  https://doi.org/10.1007/s12639-014-0641-1 CrossRefGoogle Scholar
  20. Farajzadeh S, Heshmatkhah A, Vares B et al (2016) Topical terbinafine in the treatment of cutaneous leishmaniasis: triple blind randomized clinical trial. J Parasit Dis 40:1159–1164.  https://doi.org/10.1007/s12639-014-0641-1 CrossRefPubMedGoogle Scholar
  21. Frankenburg S, Glick D, Klaus S, Barenholz Y (1998) Efficacious topical treatment for murine cutaneous leishmaniasis with ethanolic formulations of amphotericin B. Antimicrob Agents Chemother 42:3092–3096CrossRefGoogle Scholar
  22. Freitas-Junior LH, Chatelain E, Kim HA, Siqueira-Neto JL (2012) Visceral leishmaniasis treatment: What do we have, what do we need and how to deliver it? Int J Parasitol Drugs Drug Resist 2:11–19.  https://doi.org/10.1016/J.IJPDDR.2012.01.003 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Frézard F, Demicheli C, Ribeiro RR (2009) Pentavalent antimonials: new perspectives for old drugs. Molecules 14:2317–2336.  https://doi.org/10.3390/molecules14072317 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Ganguly S, Bandyopadhyay S, Sarkar A, Chatterjee M (2006) Development of a semi-automated colorimetric assay for screening anti-leishmanial agents. J Microbiol Methods 66:79–86.  https://doi.org/10.1016/J.MIMET.2005.10.011 CrossRefPubMedGoogle Scholar
  25. Gannavaram S, Bhattacharya P, Ismail N et al (2016) Modulation of innate immune mechanisms to enhance Leishmania vaccine-induced immunity: role of coinhibitory molecules. Front Immunol 7:187.  https://doi.org/10.3389/fimmu.2016.00187 CrossRefPubMedPubMedCentralGoogle Scholar
  26. Kaye P, Scott P (2011) Leishmaniasis: complexity at the host–pathogen interface. Nat Rev Microbiol 9:604–615.  https://doi.org/10.1038/nrmicro2608 CrossRefPubMedGoogle Scholar
  27. Kedzierski L, Zhu Y, Handman E (2006) Leishmania vaccines: progress and problems. Parasitology 133:S87.  https://doi.org/10.1017/S0031182006001831 CrossRefPubMedGoogle Scholar
  28. Koutsoni O, Barhoumi M, Guizani I, Dotsika E (2014) Leishmania eukaryotic initiation factor (LeIF) inhibits parasite growth in murine macrophages. PLoS ONE 9:1–10.  https://doi.org/10.1371/journal.pone.0097319 CrossRefGoogle Scholar
  29. Kremsner PG, Krishna S (2004) Combinations of anti malaria drugs—Malaria site. Lancet (London, England). https://www.malariasite.com/antimalarial-combinations/. Accessed 11 Jun 2018
  30. Kumar R, Engwerda C (2014) Vaccines to prevent leishmaniasis. Clin Transl Immunol 3:e13.  https://doi.org/10.1038/cti.2014.4 CrossRefGoogle Scholar
  31. Lee N, Bertholet S, Debrabant A et al (2002) Programmed cell death in the unicellular protozoan parasite Leishmania. Cell Death Differ 9:53–64.  https://doi.org/10.1038/sj.cdd.4400952 CrossRefPubMedGoogle Scholar
  32. Lira R, Sundar S, Makharia A et al (1999) Evidence that the high incidence of treatment failures in Indian Kala-Azar is due to the emergence of antimony-resistant strains of Leishmania donovani. J Infect Dis 180:564–567.  https://doi.org/10.1086/314896 CrossRefPubMedGoogle Scholar
  33. Lobanov AV, Gromer S, Salinas G, Gladyshev VN (2016) Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein. Nucl Acids Res 1:1.  https://doi.org/10.1093/nar/gkl541 CrossRefGoogle Scholar
  34. Mahale NB, Thakkar PD, Mali RG et al (2012) Niosomes: novel sustained release nonionic stable vesicular systems—an overview. Adv Colloid Interface Sci 183–184:46–54.  https://doi.org/10.1016/j.cis.2012.08.002 CrossRefPubMedGoogle Scholar
  35. Mahmoudvand H, Shakibaie M, Tavakoli R et al (2014) In vitro study of leishmanicidal activity of biogenic selenium nanoparticles against Iranian isolate of sensitive and glucantime-resistant Leishmania tropica. Iran J Parasitol 9:452–460PubMedPubMedCentralGoogle Scholar
  36. Martín-Montes Á, Plano D, Martín-Escolano R et al (2017) Library of seleno-compounds as novel agents against Leishmania species. Antimicrob Agents Chemother 61:1–13.  https://doi.org/10.1128/AAC.02546-16 CrossRefGoogle Scholar
  37. Mitchison D, Davies G (2012) The chemotherapy of tuberculosis: past, present and future [State of the art]. Int J Tuberc Lung Dis 16:724–732.  https://doi.org/10.5588/ijtld.12.0083 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Momeni AZ, Aminjavaheri M, Omidghaemi MR (2003) Treatment of cutaneous leishmaniasis with ketoconazole cream. J Dermatolog Treat 14:26–29CrossRefGoogle Scholar
  39. Moosavian Kalat SA, Khamesipour A, Bavarsad N et al (2014) Use of topical liposomes containing meglumine antimoniate (Glucantime) for the treatment of L. major lesion in BALB/c mice. Exp Parasitol 143:5–10.  https://doi.org/10.1016/j.exppara.2014.04.013 CrossRefGoogle Scholar
  40. Murray HW, Flanders KC, Debra D et al (2005) Antagonizing deactivating cytokines to enhance host defense and chemotherapy in experimental visceral leishmaniasis antagonizing deactivating cytokines to enhance host defense and chemotherapy in experimental visceral leishmaniasis. Infect Immun 73:3903–3911.  https://doi.org/10.1128/IAI.73.7.3903 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Olliaro PL, Taylor WRJ (2003) Antimalarial compounds: from bench to bedside. J Exp Biol 206:3753–3759CrossRefGoogle Scholar
  42. Omollo R, Alexander N, Edwards T et al (2011) Safety and efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial. Trials 12:166.  https://doi.org/10.1186/1745-6215-12-166 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Osorio LE, Palacios R, Chica ME, Ochoa MT (1998) Treatment of cutaneous leishmaniasis in Colombia with dapsone. Lancet 351:498–499.  https://doi.org/10.1016/S0140-6736(05)78687-6 CrossRefPubMedGoogle Scholar
  44. Owais M, Gupta C (2005) Targeted drug delivery to macrophages in parasitic infections. Curr Drug Deliv 2:311–318.  https://doi.org/10.2174/156720105774370177 CrossRefPubMedGoogle Scholar
  45. Perez AP, Altube MJ, Schilrreff P et al (2016) Topical amphotericin B in ultradeformable liposomes: formulation, skin penetration study, antifungal and antileishmanial activity in vitro. Colloids Surf B Biointerfaces 139:190–198.  https://doi.org/10.1016/j.colsurfb.2015.12.003 CrossRefPubMedGoogle Scholar
  46. Prajapati VK, Awasthi K, Gautam S et al (2011) Targeted killing of Leishmania donovani in vivo and in vitro with amphotericin B attached to functionalized carbon nanotubes. J Antimicrob Chemother 66:874–879.  https://doi.org/10.1093/jac/dkr002 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Raina P, Kaur S (2012) Knockdown of LdMC1 and Hsp70 by antisense oligonucleotides causes cell-cycle defects and programmed cell death in Leishmania donovani. Mol Cell Biochem 359:135–149.  https://doi.org/10.1007/s11010-011-1007-y CrossRefPubMedGoogle Scholar
  48. Rayman MP (2005) Selenium in cancer prevention: a review of the evidence and mechanism of action. Proc Nutr Soc 64:527–542CrossRefGoogle Scholar
  49. Rayman MP (2012) Selenium and human health. Lancet 379:1256–1268.  https://doi.org/10.1016/S0140-6736(11)61452-9 CrossRefPubMedGoogle Scholar
  50. Riabi TR, Sharifi I, Mohammadi AM et al (2013) Evaluation of a possible synergistic effect of meglumine antimoniate with paromomycin, miltefosine or allopurinol on in vitro susceptibility of Leishmania tropica resistant isolate. Iran J Parasitol 8:396–401Google Scholar
  51. Rogerson A, Cummings J, Florence AT (1987) Adriamycin-loaded niosomes: drug entrapment, stability and release. J Microencapsul 4:321–328.  https://doi.org/10.3109/02652048709021824 CrossRefPubMedGoogle Scholar
  52. Santos DO, Coutinho CER, Madeira MF et al (2008) Leishmaniasis treatment—a challenge that remains: a review. Parasitol Res 103:1–10.  https://doi.org/10.1007/s00436-008-0943-2 CrossRefPubMedGoogle Scholar
  53. Seifert K, Croft SL (2006) In vitro and in vivo interactions between miltefosine and other antileishmanial drugs. Antimicrob Agents Chemother 50:73–79.  https://doi.org/10.1128/AAC.50.1.73-79.2006 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Shokri A, Sharifi I, Khamesipour A et al (2012) The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate. Parasitol Res 110:1113–1117.  https://doi.org/10.1007/s00436-011-2599-6 CrossRefPubMedGoogle Scholar
  55. Soflaei S, Dalimi A, Abdoli A et al (2014) Anti-leishmanial activities of selenium nanoparticles and selenium dioxide on Leishmania infantum. Comp Clin Path 23:15–20.  https://doi.org/10.1007/s00580-012-1561-z CrossRefGoogle Scholar
  56. Sundar S, Chakravarty J (2010) Liposomal amphotericin B and leishmaniasis: dose and response. J Glob Infect Dis 2:159–166.  https://doi.org/10.4103/0974-777X.62886 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Sundar S, Singh A, Singh OP (2014) Strategies to overcome antileishmanial drugs unresponsiveness. J Trop Med 2014:1–7.  https://doi.org/10.1155/2014/646932 CrossRefGoogle Scholar
  58. Thakur CP, Kanyok TP, Pandey AK et al (2000) A prospective randomized, comparative, open-label trial of the safety and efficacy of paromomycin (aminosidine) plus sodium stibogluconate versus sodium stibogluconate alone for the treatment of visceral leishmaniasis. Trans R Soc Trop Med Hyg 94(4):429–431CrossRefGoogle Scholar
  59. Tolouei S, Hasheminia S, Narimani M et al (2011) Leishmanicidal activity of films containing paromomycin and gentamicin sulfate both in vitro and in vivo. Iran J Parasitol 6:60–65PubMedPubMedCentralGoogle Scholar
  60. Torrado JJ, Espada R, Ballesteros MP, Torrado-Santiago S (2008) Amphotericin B formulations and drug targeting. J Pharm Sci 97:2405–2425.  https://doi.org/10.1002/jps.21179 CrossRefPubMedGoogle Scholar
  61. Tran PA, Webster TJ (2011) Selenium nanoparticles inhibit Staphylococcus aureus growth. Int J Nanomed 6:1553–1558.  https://doi.org/10.2147/IJN.S21729 CrossRefGoogle Scholar
  62. Varikuti S, Oghumu S, Saljoughian N et al (2017) Topical treatment with nanoliposomal amphotericin B reduces early lesion growth but fails to induce cure in an experimental model of cutaneous leishmaniasis caused by Leishmania mexicana. Acta Trop 173:102–108.  https://doi.org/10.1016/J.ACTATROPICA.2017.06.004 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Wagh VD, Deshmukh OJ (2015) Niosomes as ophthalmic drug delivery systems: a review. J Pharm Res 3:1558–1563Google Scholar
  64. Whanger PD (2004) Selenium and its relationship to cancer: an update. Br J Nutr 91:11–28CrossRefGoogle Scholar
  65. White NJ (1999) Delaying antimalarial drug resistance with combination chemotherapy. Parassitologia 41:301–308PubMedGoogle Scholar
  66. Wijnant G-J, Van Bocxlaer K, Yardley V et al (2018) Relation between skin pharmacokinetics and efficacy in Am Bisome treatment of murine cutaneous leishmaniasis. Antimicrob Agents Chemother 62:e02009-17.  https://doi.org/10.1128/aac.02009-17 CrossRefPubMedPubMedCentralGoogle Scholar
  67. World Health Organization (2012) Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis. World Health Organ Tech Rep Ser (975):v–xii, 1–100Google Scholar
  68. Yang J, Huang K, Qin S et al (2009) Antibacterial action of selenium-enriched probiotics against pathogenic Escherichia coli. Dig Dis Sci 54:246–254.  https://doi.org/10.1007/s10620-008-0361-4 CrossRefPubMedGoogle Scholar
  69. Yardley V, Croft SL (2000) A comparison of the activities of three amphotericin B lipid formulations against experimental visceral and cutaneous leishmaniasis. Int J Antimicrob Agents 13:243–248.  https://doi.org/10.1016/S0924-8579(99)00133-8 CrossRefPubMedGoogle Scholar
  70. Yazdanpanah Y, Sissoko D, Egger M et al (2004) Clinical efficacy of antiretroviral combination therapy based on protease inhibitors or non-nucleoside analogue reverse transcriptase inhibitors: indirect comparison of controlled trials. BMJ 328:249.  https://doi.org/10.1136/bmj.37995.435787.A6 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Zalila H, González IJ, El-Fadili AK et al (2011) Processing of metacaspase into a cytoplasmic catalytic domain mediating cell death in Leishmania major. Mol Microbiol 79:222–239.  https://doi.org/10.1111/j.1365-2958.2010.07443.x CrossRefPubMedPubMedCentralGoogle Scholar
  72. Zhong M, Wang X, Wen J et al (2013) Selection of reference genes for quantitative gene expression studies in the house fly (Musca domestica L.) using reverse transcription quantitative real-time PCR. Acta Biochim Biophys Sin (Shanghai) 45:1069–1073.  https://doi.org/10.1093/abbs/gmt111 CrossRefGoogle Scholar

Copyright information

© Indian Society for Parasitology 2019

Authors and Affiliations

  • Mahshid Mostafavi
    • 1
  • Saeedeh Farajzadeh
    • 2
    Email author
  • Iraj Sharifi
    • 1
  • Payam Khazaeli
    • 3
  • Hamid Sharifi
    • 4
  1. 1.Leishmaniasis Research CenterKerman University of Medical SciencesKermanIran
  2. 2.Department of Pediatric DermatologyKerman University of Medical SciencesKermanIran
  3. 3.Pharmaceutical Research Center, School of PharmacyKerman University of Medical SciencesKermanIran
  4. 4.HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in HealthKerman University of Medical SciencesKermanIran

Personalised recommendations