Skip to main content
SpringerLink
Log in

Evaluation of the efficacy of albendazole sulfoxide (ABZ-SO)–loaded chitosan-PLGA nanoparticles in the treatment of cystic echinococcosis in laboratory mice

  • Treatment and Prophylaxis - Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Albendazole is known as the drug of choice for medical treatment of cystic echinococcosis (CE). Albendazole sulfoxide (ABZ-SO), as the main active metabolite of albendazole, has low efficacy in the disease due to low water solubility and poor absorptivity. PLGA nanoparticles (NPs) enhance the dissolution of poorly soluble drugs, and chitosan (CS) coating enhances oral drug delivery of NPs. In this study, the efficacy of ABZ-SO-loaded CS-PGLA NPs in the treatment of CE was evaluated in laboratory mice. ABZ-SO-loaded CS-PGLA NPs were prepared by nanoprecipitation and characterized by dynamic light scattering method and scanning electron microscopy. Thirty mice were intraperitoneally infected by 1000 protoscoleces of Echinococcus granulosus. Ten months later, the mice were allocated into 3 groups: groups 1 and 2 were treated with ABZ-SO and ABZ-SO-loaded CS-PGLA NPs, respectively, and the mice in group 3 remained untreated as the control group. The drugs were administered by gavage for 45 days at a daily dose of 10 mg/kg. Finally, all mice were opened and the cysts were collected, counted, weighed, and measured separately. The therapeutic effect of ABZ-SO in the number, weight, and volume of the cysts were not statistically significant compared with those in ABZ-SO-loaded CS-PGLA NPs and the control group. However, the therapeutic effect of ABZ-SO-loaded CS-PGLA NPs in the weight and volume of cysts were statistically significant when compared with that in the control group (p ˂ 0.05). In conclusions, this study revealed that ABZ-SO-loaded CS-PGLA NPs could enhance the therapeutic efficacy of ABZ-SO in the treatment of CE in laboratory mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

All relevant data are within the paper and its Supporting Information files.

References

  • 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

    Article  CAS  Google Scholar 

  • Aksit D, Yalinkilinc HS, Sekkin S, Boyaciglu M, Cirak VY, Ayaz E, Gokbulut C (2015) Comparative pharmacokinetics and bioavailability of albendazole sulfoxide in sheep and goats, and dose-dependent plasma disposition in goats. BMC Vet Res 11:124

    Article  Google Scholar 

  • Arroyo G, Bustos JA, Lescano AG, Gonzales I, Saavedra H, Rodriguez S, Pretell EJ, Bonato PS, Lanchote VL, Takayanagui OM, Horton J, Gonzalez AE, Gilman RH, Garcia HH (2019) Albendazole sulfoxide plasma levels and efficacy of antiparasitic treatment in patients with parenchymal neurocysticercosis. Clin Infect Dis 69:1996–2002

    Article  CAS  Google Scholar 

  • Bao GS, Zhang H, Jing T, Qiao H, Wang J (2008) In vitro observation on albendazole sulfoxide and its enantiomers against Echinococcus granulosus protoscolex. Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi 26:459–461

    PubMed  Google Scholar 

  • Chai J, Menghebat WJ, Deyu S, Bin L, Jincao S, Chen F, Xiong L, Yiding M, Xiuling W, Dolikun G, Yanchun W, Fanghua G, Shuhua X (2004) Observations on clinical efficacy of albendazole emulsion in 264 cases of hepatic cystic echinococcosis. Parasitol Int 53:3–10

    Article  CAS  Google Scholar 

  • Crompton DWT (2012) Accelerating work to overcome the global impact of neglected tropical disease: a roadmap for implementation: executive summary. WHO, Geneva

    Google Scholar 

  • Del Cacho E, Causape C, Sanchez-Acedo C, Quilez J (1996) Cytochemical study of the germinal membrane of the Echinococcus granulosus cyst. Vet Parasitol 62:101–106

    Article  Google Scholar 

  • Elissondo MC, Bermudez JM, Ullio Gamboa GV, Pensel PE, Cid AG, Juárez MM, Allemandi DA, Palma SD (2013) Hydatid disease: current status of chemotherapy and drug delivery systems. Current Drug Therapy 8:197–205

    Article  CAS  Google Scholar 

  • Ingold K, Bigler P, Thormann W, Cavaliero T, Gottstein B, Hemphill A (1999) Efficacies of albendazole sulfoxide and albendazole sulfone against in vitro-cultivated Echinococcus multilocularis metacestodes. Antimicrob Agents Chemother 43:1052–1061

    Article  CAS  Google Scholar 

  • Jenkins DJ, Romig T, Thompson RCA (2005) Emergence/re-emergence of Echinococcus spp.: a global update. Int Journal Parasitol 35:1205–1219

    Article  CAS  Google Scholar 

  • Junghanss T, Menezes da Silva A, Horton J, Chiodini PL, Brunetti E (2008) Clinical management of cystic echinococcosis: state of the art, problems, and perspectives. Am J Trop Med Hyg 79(3):301–311

    Article  Google Scholar 

  • Kang BS, Choi JS, Lee SE, Lee JK, Kim TH, Jang WS, Tunsirikongkon A, Kim JK, Park JS (2017) Enhancing the in vitro anticancer activity of albendazole incorporated into chitosan-coated PLGA nanoparticles. Carbohydr Polym 159:39–47

    Article  CAS  Google Scholar 

  • Koziol U, Brehm K (2015) Recent advances in echinococcus genomics and stem cell research. Vet parasitol 213:92–102

    Article  CAS  Google Scholar 

  • Li T, Ito A, Pengcuo R, Sako Y, Chen X, Qiu D, Xiao N, Craig PS (2011) Post-treatment follow-up study of abdominal cystic echinococcosis in Tibetan communities of northwest Sichuan Province, China. PLoS Negl Trop Dis 5:e1364

    Article  Google Scholar 

  • Lötsch F, Naderer J, Skuhala T, Groger M, Auer H, Kaczirek K, Waneck F, Ramharter M (2016) Intra-cystic concentrations of albendazole-sulphoxide in human cystic echinococcosis: a systematic review and analysis of individual patient data. Parasitol Res 115:2995–3001

    Article  Google Scholar 

  • Manouras A, Genetzakis M, Lagoudianakis EE, Papadima A, Triantafillou C, Kekis PV, Filis K, Katergiannakis V (2007) Intact germinal layer of liver hydatid cysts removed after administration of albendazole. Neth J Med 65:112–116

    CAS  PubMed  Google Scholar 

  • McManus DP, Zhang W, Li J, Bartley PB (2003) Echinococcosis. Lancet 362:1295–1304

    Article  Google Scholar 

  • McManus DP, Gray DJ, Zhang W, Yang Y (2012) Diagnosis, treatment, and management of echinococcosis. Bmj 344:e3866

    Article  Google Scholar 

  • Moazeni M, Larki S, Saharkhiz MJ, Oryan A, Lari MA, Alavi AM (2014) In vivo study of the efficacy of the aromatic water of Zataria multiflora on hydatid cysts. Antimicrob Agents Chemother 58:6003–6008

    Article  Google Scholar 

  • Moro P, Schantz PM (2009) Echinococcosis: a review. Int J Infect Dis 13:125–133

    Article  CAS  Google Scholar 

  • Mortezaei S, Afgar A, Mohammadi MA, Mousavi SM, Sadeghi B, Harandi MF (2019) The effect of albendazole sulfoxide on the expression of miR-61 and let-7 in different in vitro developmental stages of Echinococcus granulosus. Acta Trop 195:97–102

    Article  CAS  Google Scholar 

  • Naseri M, Akbarzadeh A, Spotin A, Akbari NAR, Mahami-Oskouei M, Ahmadpour E (2016) Scolicidal and apoptotic activities of albendazole sulfoxide and albendazole sulfoxide-loaded PLGA-PEG as a novel nanopolymeric particle against echinococcus granulosus protoscoleces. Parasitol Res 115:4595–4603

    Article  Google Scholar 

  • Nosengo N (2016) Can you teach old drugs new tricks? Nature 16:314–316

    Article  Google Scholar 

  • 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 152:185–194

    Article  CAS  Google Scholar 

  • Pensel PE, Elissondo N, Gambino G, Gamboa GU, Benoit J-P, Elissondo MC (2017) Experimental cystic echinococcosis therapy: In vitro and in vivo combined 5-fluorouracil/albendazole treatment. Vet Parasitol 245:62–70

    Article  CAS  Google Scholar 

  • Rafiei A, Soltani S, Ramezani Z, Abbaspour MR, Jelowdar A, Kahvaz MS (2019) Ultrastructural changes on fertile and infertile hydatid cysts induced by conventional and solid lipid nanoparticles of albendazole and albendazole sulfoxide. Comp Clin Pathol 28:1045–1053

    Article  CAS  Google Scholar 

  • Rohit B, Pal KI (2013) A method to prepare solid lipid nanoparticles with improved entrapment efficiency of hydrophilic drugs. Curr Nanosci 9:211–220

    Article  CAS  Google Scholar 

  • Saimot AG, Cremieux AC, Hay JM, Meulmans A, Giovanangeli MD, Delaitre B, Coulaud JP (1983) Albendazole as a potential treatment for human hydatidosis. Lancet 17:652–656

    Article  Google Scholar 

  • Senyuz OF, Yesildag E, Celayir S (2001) Albendazole therapy in the treatment of hydatid liver disease. Surg Today 2001(31):487–491

    Google Scholar 

  • Skuhala T, Trkulja V, Runje M, Vukelic D, Desnica B (2014) Albendazole sulphoxide 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):146–155

    Article  CAS  Google Scholar 

  • Soltani S, Rafiei A, Ramezani Z, Abbaspour MR, Jelowdar A, Sagha Kahvaz M (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 

  • 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

    Article  Google Scholar 

  • Wen H, Vuitton L, Tuxun T, Li J, Vuitton DA, Zhang W, McManus DP (2019) Echinococcosis: advances in the 21st century. Clin Microbiol Rev 32:e00075–e00018

    Article  Google Scholar 

  • Zhang X, Sun M, Zheng A, Cao D, Bi Y, Sun J (2012) Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration. Eur J Pharma Sci 45:632–638

    Article  CAS  Google Scholar 

  • Zhang S, Zhou Y, Su L, Zhang X, Wang H, Liu B (2017) In vivo evaluation of the efficacy of combined albedazole-IFN-α treatment for cystic echinococcosis in mice. Parasitol Res 116:735–742

    Article  Google Scholar 

Download references

Acknowledgments

We acknowledge Dr. Samirasadat Abolmaali for her technical assistance during this study.

Funding

This work was supported by Iran National Science Foundation (INSF) (grant number: 96002976) and Shiraz University (grant number: 96GCU2M1346).

Author information

Authors and Affiliations

  1. Department of Parasitology, Division of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, 713451731, Iran

    Mohammad Mahdi Darvishi & Mohammad Moazeni

  2. Department of Pharmaceutical Nanotechnology, Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Marzieh Alizadeh, Mehdi Abedi & Ali-Mohammad Tamaddon

Authors
  1. Mohammad Mahdi Darvishi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mohammad Moazeni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marzieh Alizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mehdi Abedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ali-Mohammad Tamaddon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Mohammad Moazeni or Ali-Mohammad Tamaddon.

Ethics declarations

This study conformed to the guidelines for the care and use of laboratory animals established by the Ethics Committee of Shiraz University with permit number 96GCU2M1346. Unnecessary animal suffering was avoided throughout the study.

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Section Editor: Christoph G. Grevelding

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 219 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Darvishi, M.M., Moazeni, M., Alizadeh, M. et al. Evaluation of the efficacy of albendazole sulfoxide (ABZ-SO)–loaded chitosan-PLGA nanoparticles in the treatment of cystic echinococcosis in laboratory mice. Parasitol Res 119, 4233–4241 (2020). https://doi.org/10.1007/s00436-020-06901-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-020-06901-2

Keywords

Search

Navigation