Comparative Clinical Pathology

, Volume 28, Issue 4, pp 1045–1053 | Cite as

Ultrastructural changes on fertile and infertile hydatid cysts induced by conventional and solid lipid nanoparticles of albendazole and albendazole sulfoxide

  • Abdollah Rafiei
  • Shahrzad SoltaniEmail author
  • Zahra Ramezani
  • Mohammad Reza Abbaspour
  • Ali Jelowdar
  • Mehdi Sagha Kahvaz
Original Article


Cystic echinococcosis (CE), a serious public health problem worldwide, is caused by the larval stage of Echinococcus granulosus (E. granulosus). Despite recent progress in the CE medical treatment, this subject still remains as a priority of research. Albendazole (ABZ) is a drug of choice for the treatment of hydatidosis. Its use as an antiparasitic agent with the most efficacy is limited by the lack of water solubility. Therefore, the aim of the present study was to compare in vitro efficacy of free and solid lipid nanoparticles (SLNs) of ABZ and albendazole sulfoxide (ABZSO) against fertile and infertile hydatid cysts in terms of ultrastructural changes. ABZ-SLN and ABZSO-SLN were produced by micro emulsification and high shear homogenization technique and the physicochemical characterization of the product was evaluated. Then, the structural alterations occurring due to treatment with free and SLN formulations against fertile and infertile sheep liver hydatid cysts were assessed by optical and transmission electron microscopy (TEM) examinations. Untreated control groups revealed the typical appearance of hydatid cysts; in contrast, all treated cysts exhibited degenerative alterations with various rates. Loading ABZ and ABZSO into SLN leads to greater structural changes. In both prepared formulations, better efficacy was observed in fertile and small cysts.


Hydatidosis Albendazole Albendazole sulfoxide SLN TEM 



The authors extend their thanks to the Health Research Institute, Infectious and Tropical Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences and Department of Pharmaceutics of the College of Pharmacy. The authors are grateful to Dr. Masoud Foroutan for his helpful consultation and comments on the manuscript.

Author contributions

Conceptualization: A. Rafiei, S. Soltani, and M.R. Abbaspour; data analysis: S. Soltani and M. Sagha Kahvaz; investigation: A. Rafiei, S. Soltani, Z. Ramezani, and M.R. Abbaspour; methodology: S. Soltani, Z. Ramezani, M.R. Abbaspour, and A. Jelowdar; project administration: A. Rafiei and Z. Ramezani; supervision: A. Rafiei and Z. Ramezani; writing—original draft: A. Rafiei1, S. Soltani, Z. Ramezani, M.R. Abbaspour, and A. Jelowdar; writing—review and editing: A. Rafiei1, S. Soltani, and Z. Ramezani.


This work was financially supported by grant No. OG-93124 from the vice chancellor for research affairs of Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Agudelo Higuita NI, Brunetti E, McCloskey C (2016) Cystic echinococcosis. J Clin Microbiol 54(3):518–523. CrossRefGoogle Scholar
  2. Ahmadnia S, Moazeni M, Mohammadi-Samani S, Oryan A (2013) In vivo evaluation of the efficacy of albendazole sulfoxide and albendazole sulfoxide loaded solid lipid nanoparticles against hydatid cyst. Exp Parasitol 135(2):314–319. CrossRefGoogle Scholar
  3. Brunetti E, Kern P, Vuitton DA, Writing Panel for the W-I (2010) Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans. Acta Trop 114(1):1–16. CrossRefGoogle Scholar
  4. Budke CM, Deplazes P, Torgerson PR (2006) Global socioeconomic impact of cystic echinococcosis. Emerg Infect Dis 12(2):296–303. CrossRefGoogle Scholar
  5. Budke CM et al (2013) A systematic review of the literature on cystic echinococcosis frequency worldwide and its associated clinical manifestations. Am J Trop Med Hyg 88(6):1011–1027. CrossRefGoogle Scholar
  6. Ceballos L, Elissondo C, Moreno L, Dopchiz M, Sánchez Bruni S, Denegri G, Alvarez L, Lanusse C (2008) Albendazole treatment in cystic echinococcosis: pharmacokinetics and clinical efficacy of two different aqueous formulations. Parasitol Res 103(2):355–362. CrossRefGoogle Scholar
  7. Ceballos L, Elissondo C, Sanchez Bruni S, Denegri G, Lanusse C, Alvarez L (2011) Comparative performances of flubendazole and albendazole in cystic echinococcosis: ex vivo activity, plasma/cyst disposition, and efficacy in infected mice. Antimicrob Agents Chemother 55(12):5861–5867. CrossRefGoogle Scholar
  8. Coelho JF, Ferreira PC, Alves P, Cordeiro R, Fonseca AC, Góis JR, Gil MH (2010) Drug delivery systems: advanced technologies potentially applicable in personalized treatments. EPMA J 1(1):164–209. CrossRefGoogle Scholar
  9. Craig PS, McManus DP, Lightowlers MW, Chabalgoity JA, Garcia HH, Gavidia CM, Gilman RH, Gonzalez AE, Lorca M, Naquira C, Nieto A, Schantz PM (2007) Prevention and control of cystic echinococcosis. Lancet Infect Dis 7(6):385–394. CrossRefGoogle Scholar
  10. Dolatabadi JEN, Jamali AA, Hasanzadeh M, Omidi Y (2011) Quercetin delivery into cancer cells with single walled carbon nanotubes. Int J Biosci Biochem Bioinforma 1(1):21–25Google Scholar
  11. Dvoroznakova E, Hrckova G, Boroskova Z, Velebny S, Dubinsky P (2004) Effect of treatment with free and liposomized albendazole on selected immunological parameters and cyst growth in mice infected with Echinococcus multilocularis. Parasitol Int 53(4):315–325. CrossRefGoogle Scholar
  12. Elissondo M, Ceballos L, Dopchiz M, Andresiuk V, Alvarez L, Sánchez Bruni S, Lanusse C, Denegri G (2007) In vitro and in vivo effects of flubendazole on Echinococcus granulosus metacestodes. Parasitol Res 100(5):1003–1009. CrossRefGoogle Scholar
  13. Elissondo MC, Pensel PE, Denegri GM (2013) Could thymol have effectiveness on scolices and germinal layer of hydatid cysts? Acta Trop 125(3):251–257. CrossRefGoogle Scholar
  14. Ezzati Nazhad Dolatabadi J, Valizadeh H, Hamishehkar H (2015) Solid lipid nanoparticles as efficient drug and gene delivery systems: recent breakthroughs. Adv Pharm Bull 5(2):151–159. CrossRefGoogle Scholar
  15. Hemphill A et al (2010) Echinococcus metacestodes as laboratory models for the screening of drugs against cestodes and trematodes. Parasitology 137(3):569–587. CrossRefGoogle Scholar
  16. Ibrahim WM, AlOmrani AH, Yassin AE (2014) Novel sulpiride-loaded solid lipid nanoparticles with enhanced intestinal permeability. Int J Nanomedicine 9:129–144. Google Scholar
  17. Kelidari HR, Akbari J, Saeedi M (2013) Application and characterization of solid lipid nanoparticles and nanostructured lipid carriers as drug delivery systems. J Mazandaran Uni Med Sci 23(98):387–403Google Scholar
  18. Khademvatan S, Yousefi E, Rafiei A, Rahdar M, Saki J (2013) Molecular characterization of livestock and human isolates of Echinococcus granulosus from south-west Iran. J Helminthol 87(2):240–244. CrossRefGoogle Scholar
  19. Khademvatan S, Majidiani H, Foroutan M, Hazrati Tappeh K, Aryamand S, Khalkhali HR (2018) Echinococcus granulosus genotypes in Iran: a systematic review. J Helminthol:1–8.
  20. Khalkhali HR, Foroutan M, Khademvatan S, Majidiani H, Aryamand S, Khezri P, Aminpour A (2018) Prevalence of cystic echinococcosis in Iran: a systematic review and meta-analysis. J Helminthol 92(3):260–268. CrossRefGoogle Scholar
  21. Liu C, Zhang H, Yin J, Hu W (2015) In vivo and in vitro efficacies of mebendazole, mefloquine and nitazoxanide against cyst echinococcosis. Parasitol Res 114(6):2213–2222. CrossRefGoogle Scholar
  22. Mandal S, Mandal MD (2012) Human cystic echinococcosis: epidemiologic, zoonotic, clinical, diagnostic and therapeutic aspects. Asian Pac J Trop Med 5(4):253–260. CrossRefGoogle Scholar
  23. McManus DP, Zhang W, Li J, Bartley PB (2003) Echinococcosis. Lancet 362(9392):1295–1304. CrossRefGoogle Scholar
  24. McManus DP, Gray DJ, Zhang W, Yang Y (2012) Diagnosis, treatment, and management of echinococcosis. BMJ 344(7861):e3866. CrossRefGoogle Scholar
  25. Moro P, Schantz PM (2009) Echinococcosis: a review. Int J Infect Dis 13(2):125–133. CrossRefGoogle Scholar
  26. Morris DL, Chinnery JB, Georgiou G, Stamatakis G, Golematis B (1987) Penetration of albendazole sulphoxide into hydatid cysts. Gut 28(1):75–80CrossRefGoogle Scholar
  27. Otero-Abad B, Torgerson PR (2013) A systematic review of the epidemiology of echinococcosis in domestic and wild animals. PLoS Negl Trop Dis 7(6):e2249. CrossRefGoogle Scholar
  28. Perez-Serrano J, Denegri G, Casado N, Rodriguez-Caabeiro F (1997) In vivo effect of oral albendazole and albendazole sulphoxide on development of secondary echinococcosis in mice. Int J Parasitol 27(11):1341–1345CrossRefGoogle Scholar
  29. Ravichandran R (2010) In vivo pharmacokinetic studies of albendazole nanoparticulate oral formulations for improved bioavailability. Int J Green Nanotechnol Biomed 2(1):B46–B53. Google Scholar
  30. Rostami E, Kashanian S, Azandaryani AH, Faramarzi H, Dolatabadi JEN, Omidfar K (2014) Drug targeting using solid lipid nanoparticles. Chem Phys Lipids 181:56–61. CrossRefGoogle Scholar
  31. Sadjjadi SM (2006) Present situation of echinococcosis in the Middle East and Arabic North Africa. Parasitol Int 55(Suppl):S197–S202. CrossRefGoogle Scholar
  32. Skuhala T, Trkulja V, Runje M, Vukelic D, Desnica B (2014) Albendazolesulphoxide concentrations in plasma and hydatid cyst and prediction of parasitological and clinical outcomes in patients with liver hydatidosis caused by Echinococcus granulosus. Croat Med J 55(2):146–155CrossRefGoogle Scholar
  33. Soltani S, Rafiei A, Ramezani Z, Abbaspour MR, Jelowdar A, Kahvaz MS (2017) Evaluation of the hydatid cyst membrane permeability of albendazole and albendazole sulfoxide-loaded solid lipid nanoparticles. Jundishapur J Nat Pharm Prod 12(2):e34723. Google Scholar
  34. de Souza MC, Marchetti JM (2012) Development of albendazole sulfoxide-loaded Eudragit microparticles: a potential strategy to improve the drug bioavailability. Adv Powder Technol 23(6):801–807CrossRefGoogle Scholar
  35. Stojkovic M, Zwahlen M, Teggi A, Vutova K, Cretu CM, Virdone R, Nicolaidou P, Cobanoglu N, Junghanss T (2009) Treatment response of cystic echinococcosis to benzimidazoles: a systematic review. PLoS Negl Trop Dis 3(9):e524. CrossRefGoogle Scholar
  36. Torgerson PR, Devleesschauwer B, Praet N, Speybroeck N, Willingham AL, Kasuga F, Rokni MB, Zhou XN, Fèvre EM, Sripa B, Gargouri N, Fürst T, Budke CM, Carabin H, Kirk MD, Angulo FJ, Havelaar A, de Silva N (2015) World Health Organization estimates of the global and regional disease burden of 11 foodborne parasitic diseases, 2010: a data synthesis. PLoS Med 12(12):e1001920. CrossRefGoogle Scholar
  37. Truong Cong T et al (2008) Study on the hydatid cyst membrane: permeation of model molecules and interactions with drug-loaded nanoparticles. Int J Pharm 353(1–2):223–232. CrossRefGoogle Scholar
  38. Verma VC, Gangwar M, Yashpal M, Nath G (2013) Anticestodal activity of endophytic Pestalotiopsis sp. on protoscoleces of hydatid cyst Echinococcus granulosus. Biomed Res Int 2013:308515. Google Scholar
  39. Wu XW, Chen XL, Zhang SJ, Zhang X, Sun H, Peng XY (2011) Pericyst may be a new pharmacological and therapeutic target for hydatid disease. Chin Med J 124(18):2857–2862Google Scholar
  40. Yones DA, Taher GA, Ibraheim ZZ (2011) In vitro effects of some herbs used in Egyptian traditional medicine on viability of protoscolices of hydatid cysts. Korean J Parasitol 49(3):255–263. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  • Abdollah Rafiei
    • 1
    • 2
  • Shahrzad Soltani
    • 3
    Email author
  • Zahra Ramezani
    • 4
  • Mohammad Reza Abbaspour
    • 5
  • Ali Jelowdar
    • 2
  • Mehdi Sagha Kahvaz
    • 3
  1. 1.Health Research Institute, Infectious and Tropical Diseases Research CenterAhvaz Jundishapur University of Medical SciencesAhvazIran
  2. 2.Department of Parasitology, School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
  3. 3.Abadan School of Medical SciencesAbadanIran
  4. 4.Nanotechnology Research Center, School of PharmacyAhvaz Jundishapur University of Medical SciencesAhvazIran
  5. 5.Targeted Drug Delivery Research Center, School of PharmacyMashhad University of Medical SciencesMashhadIran

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