Journal of Parasitic Diseases

, Volume 43, Issue 4, pp 658–671 | Cite as

Evaluation of the therapeutic efficacy of albendazole-loaded silver nanoparticles against Echinococcus granulosus infection in experimental mice

  • Nashaat E. Nassef
  • Abdel-Gawad E. Saad
  • Nancy M. Harba
  • Engy V. N. BeshayEmail author
  • Marwa A. Gouda
  • Sawsan S. Shendi
  • Asmaa Shams El-Dein Mohamed
Original Article


The drug of choice for treatment of hydatid disease, albendazole (ABZ) is a poorly water-soluble drug; thus, enhancing its solubility is required. Among metal nanoparticles (NPs), silver (Ag) NPs showed antimicrobial efficacies. Therefore, this study was conducted to evaluate nanosilver particles (Ag NPs) free or combined with albendazole against Echinococcus granulosus infection in vivo. In this study, besides the normal control group (GI) (n = 5), 80 mice were infected with 2000 viable protoscoleces intraperitoneally then divided equally (n = 20) into the infected control (GII), ABZ-treated (GIII), nanosilver-treated (GIV) and ABZ-loaded-Ag NPs-treated (GV) groups. On the 90th post-infection day, treatment was started and continued for 8 weeks then the experiment was terminated. Each mouse was subjected to measurement of hydatid cysts’ sizes and weights, serum IFN-γ, liver enzymes; histopathological and transmission electron microscopy studies. In all treated groups, there were significant reductions of hydatid cysts’ sizes and weights; however, the highest efficacy rate (63.9%) was detected in group V associated with obvious ultrastructure alterations of the cysts. The liver tissues of group II showed intense granulomatous reactions, congestion, fibrosis, necrosis and steatosis associated with significant increases in serum IFN-γ and liver enzymes. Interestingly, the best antiparasitic effect and the most significant reduction of IFN-γ towards the normal values were found in GV. Moreover, Ag NPs had reduced the toxic effects of ABZ such as necrosis, steatosis and the elevated serum liver enzymes. Therefore, loading ABZ on Ag NPs could be a potential method to improve ABZ efficacy against hydatid disease.


Albendazole E. granulosus IFN-γ In vivo Nanosilver particles Ultrastructure 



The authors would acknowledge Prof. Ibrahim Shalash, the professor of Parasitology and Immunology at Theodor Bilharz Research Institute for his help in preparation of the nanoparticles.

Author’s Contribution

EVNB and SSS put the idea of the study. All authors prepared the research protocol and the study design. SSS isolated E. granulosus protoscoleces from hydatid cysts, carried out the experimental infection in mice, administrated the therapeutic doses, follow up of the mice, the parasitological study and tissue sampling. SSS and MAG performed mice sacrificing and collected the blood samples from mice, separated sera and carried out the measurement of liver enzymes and serum IFN-γ. ASEDM examined the stained liver sections and interpreted the histopathological results. SSS and EVNB interpreted the transmission electron microscopy results. SSS collected and tabulated the data while NEN, AES, NMH and EVNB participated in analysis and interpretation of the data. EVNB prepared and wrote the manuscript. All authors had read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

Authors declare that there is no conflict of interest regarding the publication of this paper.


  1. 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):314–319PubMedGoogle Scholar
  2. Al-Kuraishi AH (2009) Histopathological changes of experimental hydatidosis in liver and spleen of albino mice: age and sex effect. J Fac Med 51(4):423–428Google Scholar
  3. Amri M, Ait-Aissa S, Belguendouz H, Mezioug D, Touil-Boukoffa C (2007) In vitro antihydatic action of IFN-γ is dependent on the nitric oxide pathway. J Interferon Cytokine Res 27(9):781–787PubMedGoogle Scholar
  4. Beigh AB, Darzi MM, Bashir S, Shah A, Shah SA (2017) Gross and histopathological alterations associated with cystic echinococcosis in small ruminants. J Parasit Dis 41(4):1028–1033PubMedPubMedCentralGoogle Scholar
  5. Bhol KC, Schechter PJ (2007) Effects of nanocrystalline silver (NPI 32101) in a rat model of ulcerative colitis. Dig Dis Sci 52(10):2732–2742PubMedGoogle Scholar
  6. Burduşel AC, Gherasim O, Grumezescu AM, Mogoantă L, Ficai A, Andronescu E (2018) Biomedical applications of silver nanoparticles: an up-to-date overview. Nanomaterials 8(9):681PubMedCentralGoogle Scholar
  7. Drury RA, Wallington EA (1980) Carleton’s histopathological techniques, 5th edn. Oxford University Press, Oxford, pp 129–130Google Scholar
  8. Elissondo M, Dopchiz M, Ceballos L, Alvarez L, Bruni SS, Lanusse C, Denegri G (2006) In vitro effects of flubendazole on Echinococcus granulosus protoscoleces. Parasitol Res 98(4):317–323PubMedGoogle Scholar
  9. Elissondo MC, Bermudez JM, Ullio Gamboa GV, Pensel PE, Cid AG, Juarez MM, Allemandi DA, Palma SD (2013) Hydatid disease: current status of chemotherapy and drug delivery systems. Curr Drug Ther 8(3):197–205Google Scholar
  10. Farhadi M, Haniloo A, Rostamizadeh K, Faghihzadeh S (2018) Efficiency of flubendazole-loaded mPEG-PCL nanoparticles: a promising formulation against the protoscoleces and cysts of Echinococcus granulosus. Acta Trop 187:190–200PubMedGoogle Scholar
  11. Grosso G, Gruttadauria S, Biondi A, Marventano S, Mistretta A (2012) Worldwide epidemiology of liver hydatidosis including the Mediterranean area. World J Gastroenterol 18(13):1425PubMedPubMedCentralGoogle Scholar
  12. Higuita NIA, Brunetti E, McCloskey C (2016) Cystic echinococcosis. J Clin Microbiol 54(3):518–523Google Scholar
  13. Horton J (2018) Echinococcosis and albendazole: a case for suitable treatment. Am J Trop Med Hyg 99(4):811–812PubMedPubMedCentralGoogle Scholar
  14. Jelowdar A, Rafiei A, Abbaspour MR, Rashidi I, Rahdar M (2017) Efficacy of combined albendazol and praziquntel and their loaded solid lipid nanoparticles components in chemoprophylaxis of experimental hydatidosis. Asian Pac J Trop Biomed 7(6):549–554Google Scholar
  15. Kandeel A, Ahmed ES, Helmy H, El Setouhy M, Craig PS, Ramzy RM (2004) A retrospective hospital study of human cystic echinococcosis in Egypt. East Mediterr Health J 10(3):349–357PubMedGoogle Scholar
  16. Küster T, Stadelmann B, Aeschbacher D, Hemphill A (2014) Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model. Int J Antimicrob Agents 43(4):335–342PubMedGoogle Scholar
  17. Liang W, Wang XC, Wu XW, Zhang SJ, Sun H, Ma X, Peng XY (2014) Efficacy of albendazole chitosan microspheres against Echinococcus granulosus infection in mice. Chin J Parasitol Parasit Dis 32(3):188–192Google Scholar
  18. Liang J, Li R, He Y, Ling C, Wang Q, Huang Y, Qin J, Lu W, Wang J (2018) A novel tumor-targeting treatment strategy uses energy restriction via co-delivery of albendazole and nanosilver. Nano Res 11(9):4507–4523Google Scholar
  19. Loeschner K, Hadrup N, Qvortrup K, Larsen A, Gao X, Vogel U, Mortensen A, Lam HR, Larsen EH (2011) Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate. Part Fibre Toxicol 8(1):18PubMedPubMedCentralGoogle Scholar
  20. Luo Y, Zhang G, Liu X, Yuan M, Gao Q, Gao H, Ke L, Zhang X, Shi Y, Ma X, Zhang L (2018) Therapeutic and immunoregulatory effects of water-soluble alkaloids E2-a from Sophora moorcroftiana seeds as a novel potential agent against echinococcosis in experimentally protoscolex-infected mice. Vet Res 49(1):100PubMedPubMedCentralGoogle Scholar
  21. McManus DP, Gray DJ, Zhang W, Yang Y (2012) Diagnosis, treatment, and management of echinococcosis. BMJ 344:e3866PubMedGoogle Scholar
  22. Moro P, Schantz PM (2009) Echinococcosis: a review. Int J Infect Dis 13(2):125–133PubMedGoogle Scholar
  23. Noorani L, Stenzel M, Liang R, Pourgholami MH, Morris DL (2015) Albumin nanoparticles increase the anticancer efficacy of albendazole in ovarian cancer xenograft model. J Nanobiotechnol 13(1):25Google Scholar
  24. Nunnari G, Pinzone MR, Gruttadauria S, Celesia BM, Madeddu G, Malaguarnera G, Pavone P, Cappellani A, Cacopardo B (2012) Hepatic echinococcosis: clinical and therapeutic aspects. World J Gastroenterol 13:1448Google Scholar
  25. Palomares F, Palencia G, Ambrosio JR, Ortiz A, Jung-Cook H (2006) Evaluation of the efficacy of albendazole sulphoxide and praziquantel in combination on Taenia crassiceps cysts: in vitro studies. J Antimicrob Chemother 57(3):482–488PubMedGoogle Scholar
  26. Pensel PE, Gamboa GU, Fabbri J, Ceballos L, Bruni SS, Alvarez LI, Allemandi D, Benoit JP, Palma SD, Elissondo MC (2015) Cystic echinococcosis therapy: albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice. Acta Trop 152:185–194PubMedGoogle Scholar
  27. Pensel P, Paredes A, Albani CM, Allemandi D, Bruni SS, Palma SD, Elissondo MC (2018) Albendazole nanocrystals in experimental alveolar echinococcosis: enhanced chemoprophylactic and clinical efficacy in infected mice. Vet Parasitol 251:78–84PubMedGoogle Scholar
  28. Rahimi MT, Ahmadpour E, Esboei BR, Spotin A, Koshki MHK, Alizadeh A, Honary S, Barabadi H, Mohammadi MA (2015) Scolicidal activity of biosynthesized silver nanoparticles against Echinococcus granulosus protoscolices. Int J Surg 19:128–133PubMedGoogle Scholar
  29. Rai M, Ingle AP, Paralikar P, Gupta I, Medici S, Santos CA (2017) Recent advances in use of silver nanoparticles as antimalarial agents. Int J Pharm 526(1–2):254–270PubMedGoogle Scholar
  30. Ramachandran R, Kakar S (2009) Histological patterns in drug-induced liver disease. J Clin Pathol 62(6):481–492PubMedGoogle Scholar
  31. Rigano R, Profumo E, Ioppolo S, Notargiacomo S, Ortona E, Teggi A, Siracusano A (1995) Immunological markers indicating the effectiveness of pharmacological treatment in human hydatid disease. Clin Exp Immunol 102(2):281–285PubMedPubMedCentralGoogle Scholar
  32. Rogan MT (1998) T-cell activity associated with secondary infections and implanted cysts of Echinococcus granulosus in BALB/c mice. Parasite Immunol 20(11):527–533PubMedGoogle Scholar
  33. Rostami-Rad S, Jafari R, Yousofi-Darani H (2018) Th1/Th2-type cytokine profile in C57 black mice inoculated with live Echinococcus granulosus protoscolices. J Infect Public Health 11(6):834–839PubMedGoogle Scholar
  34. Said DE, Elsamad LM, Gohar YM (2012) Validity of silver, chitosan, and curcumin nanoparticles as anti-Giardia agents. Parasitol Res 111(2):545–554PubMedGoogle Scholar
  35. Shanmugasundaram T, Radhakrishnan M, Gopikrishnan V, Kadirvelu K, Balagurunathan R (2017) Biocompatible silver, gold and silver/gold alloy nanoparticles for enhanced cancer therapy: in vitro and in vivo perspectives. Nanoscale 9(43):16773–16790PubMedGoogle Scholar
  36. Singh BB, Sharma JK, Tuli A, Sharma R, Bal MS, Aulakh RS, Gill JPS (2014) Prevalence and morphological characterisation of Echinococcus granulosus from north India. J Parasit Dis 38(1):36–40PubMedGoogle Scholar
  37. Siracusano A, Riganò R, Ortona E, Profumo E, Margutti P, Buttari B, Delunardo F, Teggi A (2008) Immunomodulatory mechanisms during Echinococcus granulosus infection. Exp Parasitol 119(4):483–489PubMedGoogle Scholar
  38. Solcan C, Solcan G, Ioniţă M, Hristescu DV, Mitrea IL (2010) Histological aspects of cystic echinococcosis in goats. Sci Parasitol 11(4):191–198Google Scholar
  39. Solomon SD, Bahadory M, Jeyarajasingam AV, Rutkowsky SA, Boritz C, Mulfinger L (2007) Synthesis and study of silver nanoparticles. J Chem Edu 84(2):322–325Google Scholar
  40. 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):e34723Google Scholar
  41. 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):e524PubMedPubMedCentralGoogle Scholar
  42. Touil-Boukoffa C, Bauvois B, Sancéau J, Hamrioui B, Wietzerbin J (1998) Production of nitric oxide (NO) in human hydatidosis: relationship between nitrite production and interferon-γ levels. Biochimie 80(8–9):739–744PubMedGoogle Scholar
  43. Urrea-Paris MA, Moreno MJ, Casado N, Rodriguez-Caabeiro F (2002) Relationship between the efficacy of praziquantel treatment and the cystic differentiation in vivo of Echinococcus granulosus metacestode. Parasitol Res 88(1):26–31PubMedGoogle Scholar
  44. Wang W, Li J, Yao J, Wang T, Li S, Zheng X, Duan L, Zhang W (2017) In vitro and in vivo efficacies of novel carbazole aminoalcohols in the treatment of cystic echinococcosis. J Antimicrob Chemother 72(11):3122–3130PubMedGoogle Scholar

Copyright information

© Indian Society for Parasitology 2019

Authors and Affiliations

  1. 1.Medical Parasitology Department, Faculty of MedicineMenoufia UniversityShebin El-KomEgypt
  2. 2.Clinical and Molecular Parasitology Department, National Liver InstituteMenoufia UniversityShebin El-KomEgypt
  3. 3.Pathology Department, Faculty of MedicineMenoufia UniversityShebin El-KomEgypt

Personalised recommendations