In vitro and in vivo effects of chitosan-praziquantel and chitosan-albendazole nanoparticles on Echinococcus granulosus Metacestodes
- 338 Downloads
Cystic echinococcosis (CE), which is caused by the metacestode of Echinococcus granulosus, is one of the most important zoonoses affecting humans. Benzimidazoles (in particular albendazole) and praziquantel (PZQ) are effective against CE, but poor water solubility of these agents often leads to inadequate results. Here, we evaluate the effects of chitosan-albendazole (ChABZ) and chitosan-praziquantel (ChPZQ) nanoparticles as a new formulation on hydatid cysts both in vitro and in vivo. Developed microcysts in culture were treated with different concentrations of ChABZ and ChPZQ nanoparticles (either alone or in combination), and ABZ + PZQ suspension. The viability rate of microcysts was used to evaluate the drug efficacies. In addition, the prophylactic and therapeutic effects of the drugs were studied on infected DBA/2 mice. Transmission electron microscopy was used to observe the ultra-structural changes. The viability rate of microcysts and differences in cyst weights were compared by ANOVA, and the cyst numbers were compared using the Kruskal-Wallis test. The combination of ChABZ + ChPZQ nanoparticles was more effective than the ABZ + PZQ suspension in vitro (p < 0.05). In prophylaxy, a significant reduction was observed both in size and in number of the cysts in ChABZ + ChPZQ nanoparticle groups compared with the control group (p < 0.05). In the therapeutic stage, however, this treatment only reduced the cyst numbers. Degeneration of the microcysts treated with the drugs was evident in the ultra-structural imaging. Overall, the nanoparticulate drugs were more effective than their suspension counterparts, but further studies are recommended to evaluate the full potential of these nanoparticles in the treatment of human CE.
KeywordsAlbendazole Praziquantel Chitosan nanoparticles Hydatid cysts Treatment
The authors wish to thank Dr. M.C. Elissondo (National Scientific and technical Research Council, Argentina) for helpful and constructive comments. We are also grateful to Dr. Vahid Pirhajati (Iran University of Medical Sciences, Iran) for the technical assistance with the transmission electronic microscopy. Last but not least, we would like to thank Dr. Mehrdad Pedram (Dept. of Genetics and Molecular Medicine, ZUMS) for his science editing and English skills helping us for preparing and proofreading the manuscript.
This study was financially supported by Zanjan University of Medical Sciences (A-12-95-7).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
- Abulaihaiti M, Wu XW, Qiao L, Lv HL, Zhang HW, Aduwayi N, Wang YJ, Wang XC, Peng XY (2015) Efficacy of albendazole-chitosan microsphere-based treatment for alveolar echinococcosis in mice. PLoS Negl Trop Dis 9:e0003950. https://doi.org/10.1371/journal.pntd.0003950 CrossRefPubMedPubMedCentralGoogle Scholar
- 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 135:314–319. https://doi.org/10.1016/j.exppara.2013.07.017 CrossRefPubMedGoogle Scholar
- Casado N, PerezSerrano J, Denegri G, Rodriguez-Caabeiro F (1996) Development of a chemotherapeutic model for the in vitro screening of drugs against Echinococcus granulosus cysts: the effects of an albendazole albendazole sulphoxide combination. Int J Parasitol 26:59–65. https://doi.org/10.1016/0020-7519(95)00095-X CrossRefPubMedGoogle Scholar
- Choi B, Jo DH, Anower AKMM, Islam SMS, Sohn S (2016) Chitosan as an immunomodulating adjuvant on T-cells and antigen-presenting cells in herpes simplex virus type 1 infection. Mediat Inflamm. https://doi.org/10.1155/2016/4374375
- Elissondo MC, Ceballos L, Alvarez L, Bruni SS, Lanusse C, Denegri G (2009) Flubendazole and ivermectin in vitro combination therapy produces a marked effect on Echinococcus granulosus protoscoleces and metacestodes. Parasitol Res 105:835–842. https://doi.org/10.1007/s00436-009-1469-y CrossRefPubMedGoogle Scholar
- Liang HF, Yang TF, Huang CT, Chen MC, Sung HW (2005) Preparation of nanoparticles composed of poly(gamma-glutamic acid)-poly(lactide) block copolymers and evaluation of their uptake by HepG2 cells. J Control Release 105:213–225. https://doi.org/10.1016/j.jconrel.2005.03.021 CrossRefPubMedGoogle Scholar
- Liu Y, Wang XQ, Ren WX, Chen YL, Yu Y, Zhang JK, Bawudong D, Gu JP, Xu XD, Zhang XN (2013) Novel albendazole-chitosan nanoparticles for intestinal absorption enhancement and hepatic targeting improvement in rats. J Biomed Mater Res B Appl Biomater 101B:998–1005. https://doi.org/10.1002/jbm.b.32908 CrossRefGoogle Scholar
- Ogawara K, Yoshida M, Higaki K, Toshikiro Kimura, Shiraishi K, Nishikawa M, Takakura Y, Hashida M (1999) Hepatic uptake of polystyrene microspheres in rats: effect of particle size on intrahepatic distribution. J Control Release 59:15–22. https://doi.org/10.1016/S0168-3659(99)00015-2 CrossRefPubMedGoogle Scholar
- Pensel PE, Castro S, Allemandi D, Bruni SS, Palma SD, Elissondo MC (2014) Enhanced chemoprophylactic and clinical efficacy of albendazole formulated as solid dispersions in experimental cystic echinococcosis. Vet Parasitol 203:80–86. https://doi.org/10.1016/j.vetpar.2014.01.027 CrossRefPubMedGoogle Scholar
- Rokni MB (2009) Echinococcosis/hydatidosis in Iran. Iran J Parasitol 4:1–16Google Scholar
- Sashiwa H, Aiba SI (2004) Chemically modified chitin and chitosan as biomaterials. Prog Polym Sci 29:887–908. https://doi.org/10.1016/j.progpolymsci.2004.04.001 CrossRefGoogle Scholar
- Torabi N, Dobakhti F, Haniloo A (2017) Albendazole and praziquantel chitosan nanoparticles: preparation, characterization, and in vitro release study. Iran J Sci Technol Trans Sci. https://doi.org/10.1007/s40995-017-0150-z