Parasitology Research

, Volume 118, Issue 1, pp 219–234 | Cite as

Niosomes for enhanced activity of praziquantel against Schistosoma mansoni: in vivo and in vitro evaluation

  • Hager S. ZoghrobanEmail author
  • Samy I. El-Kowrany
  • Ibrahim A. Aboul Asaad
  • Gamal M. El Maghraby
  • Kholoud A. El-Nouby
  • Mona A. Abd Elazeem
Helminthology - Original Paper


Praziquantel (PZQ) is recommended by the WHO as the first line in treatment of schistosomiasis. Unfortunately, it exhibits low oral bioavailability which can compromise its efficacy. Nanostructures showed promising potential to overcome this problem. Accordingly, the aim of this study was to investigate the effect of niosomal encapsulation of PZQ on its activity on Schistosoma mansoni in vitro and in vivo. PZQ was encapsulated in niosomal formulation comprising span 60, cholesterol with peceol being included as absorption enhancer. The in vitro work determined the schistosomicidal activity and morphological changes after incubation with drug solution or PZQ-niosomes. The in vivo study utilized infected mice which received PZQ orally as solution or as niosomes. The activity was assessed by monitoring egg and worm count in addition to histopathological and immunohistochemical studies. The in vitro studies revealed that niosomes alone caused a 30% death of adult parasites and caused completely coiled body, destruction, and peeling of tubercles and spines, with flattening and effacement of gynecophoric canal, blebbing with niosomes vesicles attached to it. Niosomes containing PZQ at a concentration of 0.001 μg/ml increased the death from 30 to 50% with the corresponding PZQ solution causing only 10% death. The in vivo study reflected of niosome-PZQ over PZQ solution as indicated from significant reduction of adult worm count, hepatic and intestinal egg depositions, hepatic granuloma size, and numbers, with marked reduction of vascular endothelial growth factor expression. The study introduced niosomes as promising carriers for enhanced activity of PZQ.


Schistosoma mansoni Praziquantel activity Niosomes Nanostructures Hepatic fibrosis 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abd El-Hady MH, Abaza BE, Fathy GM, Badawey MS, Nada SM, El-Shafei MA, Abd El-Aziz HR (2013) Impact of treatment with praziquantel supplemented by silymarin on Schistosoma mansoni- induced fibrosis in mice. PUJ 6(1):77–88Google Scholar
  2. Abdelaziz AA, Elbanna TE, Sonbol FI, Gamaleldin NM, El Maghraby GM (2015) Optimization of niosomes for enhanced antibacterial activity and reduced bacterial resistance: in vitro and in vivo evaluation. Expert Opin Drug Deliv 12:163–180CrossRefGoogle Scholar
  3. Abdel-Rahman SA (2009) Monitoring Th1 and Th2 cytokine patterns after praziquantel and mirazid treatment in experimental mansoniasis. PUJ 6(1):66–77Google Scholar
  4. Ahmad A, Ahmad R (2015) Understanding the mechanism of hepatic fibrosis and potential therapeutic approaches. Saudi J Gastroenterol 18:155–167CrossRefGoogle Scholar
  5. Angaye TCN (2016) A review on the epidemiology and control of schistosomiasis in Nigeria. J Med Health Res 1(2):1–23Google Scholar
  6. Bancroft JD, Steven A (1975) Histopathological stains and their diagnostic uses. Churchil. Livingstone, pp 1–20Google Scholar
  7. Becket G, Schep LJ, Tan MY (1999) Improvement of the in vitro dissolution of praziquantel by complexation with alpha-, beta- and gamma-cyclodextrins. Int J Pharm 179(1):65–71CrossRefGoogle Scholar
  8. Botros S, Hammam O, Mahmoud M, Bergquist R (2010) Praziquantel efficacy in mice infected with PZQ non susceptible Schistsoma mansoni isolate treated with artemether: parasitological, biochemical and immunohistochemical assessment. APMIS 118:692–702CrossRefGoogle Scholar
  9. Bruno J, Neves BJ, Andrade CH, Cravo PVL (2015) Review natural products as leads in schistosome drug discovery. Molecules 20:1872–1903CrossRefGoogle Scholar
  10. Castro N, Medina R, Sotelo J, Jung H (2000) Bioavailability of praziquantel increases with concomitant administration of food. Antimicrob Agents Chemother 44(10):2903–2904CrossRefGoogle Scholar
  11. Cheever AW (1968) Conditions affecting the accuracy of potassium hydroxide digestion in techniques for counting Schistosoma mansoni eggs in tissues. Bull WHO 39:328–331Google Scholar
  12. Cong Z, Shi Y, Peng X, Wei B, Wang Y, Li J (2017) Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel. Drug Dev Ind Pharm 43(4):558–573CrossRefGoogle Scholar
  13. De Campos AM, Sánchez A, Alonso MJ (2001) Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin. A Int J Pharm 224:159–168CrossRefGoogle Scholar
  14. de Souza ALR, Andreanib T, de Oliveirad RN, Kiill CP, dos Santosa FK (2014) In vitro evaluation of permeation, toxicity and effect of praziquantel-loaded solid lipid nanoparticles against Schistosoma mansoni as a strategy to improve efficacy of the schistosomiasis treatment. Int J Pharm 463:31–37CrossRefGoogle Scholar
  15. Dkhil MA, Bauomy AA, Diab MSM, Al-Quraishy S (2016) Protective role of selenium nanoparticles against Schistosoma mansoni induced hepatic injury in mice. Biomed Res 27(1):214–219Google Scholar
  16. Duvall RH, De Witt WB (1967) An improved perfusion technique for recovering adult schistosome from laboratory animal. Am J Trop Med Hyg 16:483–486CrossRefGoogle Scholar
  17. El-Arini SK, Leuenberger H (1998) Dissolution properties of praziquantel−PVP systems. Pharm Acta Helv 73:89–94CrossRefGoogle Scholar
  18. Elhenawy AA, Rehab H, Ashourb NN, Naglaa MS, Nirmeen M (2017) Possible antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor, in mice model of Schistosoma–induced liver fibrosis. Parasitol Int 66:545–554CrossRefGoogle Scholar
  19. El-Lakkany N, El-Din SS, Ebeid F (2012a) The use of pentoxifylline as adjuvant therapy with praziquantel down regulates profibrogenic cytokines, collagen deposition and oxidative stress in experimental schistosomiasis mansoni. Exp Parasitol 129:152–157CrossRefGoogle Scholar
  20. El-Lakkany N, Seif El-Din SH, Heikal L (2012b) Bioavailability and in vivo efficacy of a praziquantel-polyvinylpyrrolidone solid dispersion in Schistosoma mansoni-infected mice. Eur J Drug Metab Pharmacokinet 37(4):289–299CrossRefGoogle Scholar
  21. El-Sisi A, Awara W, El-Masry T (2011) Effects and mechanism of action of immunomodulating agents against schistosomiasis-induced hepatic inflammation and fibrosis in mice. Res Pharm Biotechnol 3:32–45Google Scholar
  22. Fahmy ZH, El-Shennawy AM, El-Komy W (2009) Potential antiparasitic activity of pomegranate extracts against shistosomules and mature worms of Schistosoma mansoni: in vitro and in vivo study. Aust J Basic Appl Sci 3:4634–4643Google Scholar
  23. Fallon PG, Sturrock RF, Niang AC, Doenhoff MJ (1995) Diminished susceptibility to praziquantel in a Senegal isolate of Schistosoma mansoni. Am J Trop Med Hyg 53:61–62CrossRefGoogle Scholar
  24. Frezza TF, Gremião MP, Zanotti-Magalhães EM, Magalhães LA, De Souza AL, Allegretti SM (2013) Liposomal-praziquantel: efficacy against Schistosoma mansoni in a preclinical assay. Acta Trop 128(1):70–75CrossRefGoogle Scholar
  25. Glauert AM (1974) Fixation, dehydration and embedding of biological specimens. In: AM Glauert (ed) Practical Methods in Electron Microscopy. Amsterdam Oxford, pp 77–163Google Scholar
  26. Gou HF, Chen XC, Zhu J, Jiang M, Yang Y, Cao D, Hou M (2011) Expressions of COX-2 and VEGF-C in gastric cancer: correlations with lymphangiogenesis and prognostic implications. J Exp Clin Cancer Res 30(1):14CrossRefGoogle Scholar
  27. Gryseels B, Polman K, Clerinx J (2006) Human schistosomiasis. Lancet 368:1106–1118CrossRefGoogle Scholar
  28. Inagaki Y, Nemoto T, Kushida M, Sheng Y, Higashi K (2003) Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice. Hepatol 38:890–899CrossRefGoogle Scholar
  29. Ismail M, Metwally A, Farghaly A, Bruce J, Tao L, Bennet JL (1996) Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel. Am J Trop Med Hyg 55:241–218CrossRefGoogle Scholar
  30. Issa RM (2007) Schistosoma mansoni: the prophylactic and curative effects of propolis in experimentally-infected mice. Rawal Med J 32:94–98Google Scholar
  31. Jacobs W, Bogers J, Deelder A, Wery M, Marck E (1997) Adult Schistosoma mansoni worms positively modulate soluble egg antigen induced inflammatory hepatic granuloma formation in vivo. Serological analysis and immunophenotyping of extracellular matrix proteins, adhesion molecules and chemokines. Am J Pathol 150(6):2033–3045Google Scholar
  32. Kolenyak-Santos F, Garnero C, de Oliveira RN, de Souza ALR, Chorilli M (2015) Nanostructured lipid carriers as a strategy to improve the in vitro schistosomiasis activity of Praziquantel. JNN 14:1–12Google Scholar
  33. Lala S, Nandy AK, Mahato SB, Basu MK (2003) Delivery in vivo of 14-deoxy-11-oxoandrographolide, an antileishmanial agent, by different drug carriers. IJBB 40:169–174Google Scholar
  34. Lenzi JA, Mota EM, Pelajo- Machado M, Vale LS, Vale BS, Andrade ZA (2002) Intestinal fibro-vascular nodules caused by Schistosoma mansoni infection in Calomys callosus-Rengger, 1830 (Rodentia:Cricetidae): a model of concomitant fibrosis and angiogenesis. Mem Inst Oswald Cruz 97:117–127CrossRefGoogle Scholar
  35. Liang YS, Coles G, Doenhoff MJ, Vaughan RS (2001) In vitro responses of praziquantel-resistant and susceptible Schistosoma mansoni to praziquantel. Int J Parasitol 31:1227–1235CrossRefGoogle Scholar
  36. Liu Y, Meyer C, Muller A, Herweck F, Li Q et al (2012) IL-13 signaling in liver fibrogenesis. Front Immunol 3:116CrossRefGoogle Scholar
  37. Moraes J, Nascimento C, Lopes PO, Nakano E, Yamaguchi LF, Kato MJ (2013) Schistosoma mansoni: in vitro schistosomicidal activity of piplartine. Exp Parasitol 127:357–364CrossRefGoogle Scholar
  38. Mourão SC, Costa PI, Salgado HR, Gremião MP (2005) Improvement of antischistosomal activity of praziquantel by incorporation into phosphatidylcholine containing liposomes. Int J Pharm 295:157–162CrossRefGoogle Scholar
  39. Nasr M, Mansour S, Mortada ND, Elshamy AA (2008) Vesicular aceclofenac systems: a comparative study between liposomes and niosomes. J Microencapsul 25:499–512CrossRefGoogle Scholar
  40. Oliveira RN, Rehder VLG, Oliveira ASS, Montarinari-Júnior I, Carvalho JE et al (2013) Schistosoma mansoni: in vitro schistosomicidal activity of essential oil of Baccharis trimera (less) DC. Exp Parasitol 132(2):135–143CrossRefGoogle Scholar
  41. Olliaro P, Delgado-Romero P, Keiser J (2014) The little we know about the pharmacokinetics and pharmacodynamics of praziquantel (racemate and R-enantiomer). J Antimicrob Chemother 69(4):863–870CrossRefGoogle Scholar
  42. Peter PA, Warren KS (1969) A rapid method of infecting mice and other laboratory animals with Schistosoma mansoni: subcutaneous injection. J Parasitol 55:558CrossRefGoogle Scholar
  43. Rewisha E, Asel F, El Nouby KH, El-Refaie A, Baalash A (2003) Evaluation of antifibrotic effect of silymarin and myrrh on schistosomal hepatic fibrosis: an experimental study. Tanta M J 31(3):745–759Google Scholar
  44. Robert B, Jürg U, Jennifer K (2017) Controlling schistosomiasis with praziquantel: how much longer without a viable alternative? Infect Dis Poverty 6:74CrossRefGoogle Scholar
  45. Sharaf EL-Deen SA, Brakat RM, Mohamed ASE (2017) Artichoke leaf extract protects liver of Schistosoma mansoni infected mice through modulation of hepatic stellate cells recruitment. Exp Parasitol 178:51–59CrossRefGoogle Scholar
  46. Shuhua X, Binggui S, Chollet J, Utzinger J, Tanner M (2000) Tegumental changes in adult Schistosoma mansoni harbored in mice treated with artemether. J Parasitol 86:1125–1132CrossRefGoogle Scholar
  47. Smithers SR, Terry RJ (1965) The infection of laboratory hosts with cercariae of Schistosoma mansoni and the recovery of adult worms. Parasitol 55:695–710CrossRefGoogle Scholar
  48. Sultan AA, El-Gizawy SA, Osman MA, El Maghraby GM (2016) Colloidal carriers for extended absorption window of furosemide. J Pharm Pharmacol 68:324–332CrossRefGoogle Scholar
  49. Sultan AA, El-Gizawy SA, Osman MA, El Maghraby GM (2018) Niosomes for oral delivery of nateglinide: in situ-in vivo correlation. J Liposome Res 2:1–9Google Scholar
  50. WHO (2016) Summary of global update on preventive chemotherapy implementation in 2015. Wkly Epidemiol Rec 91(39):456–459Google Scholar
  51. Xie S, Pan B, Wang M, Zhu L, Wang F, Dong Z, Wang X, Zhou W (2010) Formulation, characterization and pharmacokinetics of praziquantel-loaded hydrogenated castor oil solid lipid nanoparticles. Nanomedicine 5:693–701CrossRefGoogle Scholar
  52. Yousif F, Wassel G, Boulos L, Labib T, Mahmoud K (2012) Contribution to in vitro screening of Egyptian plants for schistosomicidal activity. Pharm Biol 50(6):732–739CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Parasitology Department, Faculty of MedicineTanta UniversityTantaEgypt
  2. 2.Pharmaceutical Technology Department, Faculty of PharmacyTanta UniversityTantaEgypt
  3. 3.Pathology Department, Faculty of MedicineTanta UniversityTantaEgypt

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