OBJECTIVES: Due to Albendazole's relatively low efficacy and bioavailability, Echinococcosis has proven a challenge to manage successfully, with several studies investigating ways to improve the outcome, mainly showing mixed results. We, therefore, aimed to evaluate whether Sulfonated Graphene Oxide (S-GO), as nanocarriers, could improve the mentioned outcome. METHODS: Echinococcus protoscoleces were divided into four groups based on the agent they received, which comprised control, S-GO, Albendazole, and Albendazole-loaded S-GO (S-GO-Albendazole). Then, the Bax and Bcl-2 gene expression levels and the number of surviving protoscoleces in each group were determined. RESULTS: Bax gene expression increased by 121% in the 50 μg/ml concentration of the S-GO-Albendazole, while Bcl-2 gene expression decreased by 64%. Moreover, S-GO-Albendazole was approximately 18% more effective at neutralizing protoscoleces than Albendazole and 14% and 31% more effective at improving the expression of the mentioned genes, respectively (p < 0.05). In addition, the number of surviving protoscoleces after exposure to the mentioned concentration reduced by approximately 99%. CONCLUSIONS: S-GO, despite not having significant lethality on protoscoleces, significantly increased the lethality of Albendazole and, therefore, is a suitable nanocarrier. However, we recommend conducting in vivo and clinical studies to more accurately determine this nanocomplex's potential and side effects.

Department of Chemistry Shahid Bahonar University of Kerman Kerman 76169 Iran

Faculty of Medicine Kerman University of Medical Sciences Kerman Iran

Halal Research Center of the Islamic Republic of Iran Iran Food and Drug Administration Ministry of Health and Medical Education Tehran Iran

Medical Student of 1st Faculty of Medicine Charles University Kateřinskǎ 32 Prague 2 121 08 Czech Republic

Pathology and Stem Cell Research Center Department of Pathology School of Medicine Kerman University of Medical Sciences Kerman Iran

Research Center for Hydatid Disease in Iran Kerman University of Medical Sciences Kerman Iran

Student Research Committee Faculty of Medicine Kerman University of Medical Sciences Kerman Iran

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McManus D. P., Gray D. J., Zhang W., Yang Y. Diagnosis, treatment, and management of Echinococcosis. BMJ . 2012;344(jun11 1):p. e3866. doi: 10.1136/bmj.e3866. PubMed DOI

Budke C. M., Deplazes P., Torgerson P. R. Global socioeconomic impact of cystic Echinococcosis. Emerging Infectious Diseases . 2006;12(2):296–303. doi: 10.3201/eid1202.050499. PubMed DOI PMC

Brunetti E., Kern P., Vuitton D. A. Expert consensus for the diagnosis and treatment of cystic and alveolar Echinococcosis in humans. Acta Tropica . 2010;114(1):1–16. doi: 10.1016/j.actatropica.2009.11.001. PubMed DOI

Bloom A. K., Ryan E. T. Albendazole. In: Magill A. J., Hill D. R., Solomon T., Ryan E. T., editors. Hunter’s Tropical Medicine and Emerging Infectious Disease . London, UK: W.B. Saunders; 2013. pp. 1088–1089.

Cherry J., Demmler-Harrison G. J., Kaplan S. L., Steinbach W. J., Hotez P. J. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases E-Book: 2-Volume Set . Amsterdam, Netherlands: Elsevier Health Sciences; 2013.

Davis A., Dixon H., Pawlowski Z. S. Multicentre clinical trials of benzimidazole-carbamates in human cystic echinococcosis (phase 2) Bulletin of the World Health Organization . 1989;67(5):503–508. PubMed PMC

Horton R. J. Albendazole in treatment of human cystic Echinococcosis: 12 years of experience. Acta Tropica . 1997;64(1-2):79–93. doi: 10.1016/s0001-706x(96)00640-7. PubMed DOI

Dehkordi A. B., Sanei B., Yousefi M., et al. Albendazole and treatment of hydatid cyst: review of the literature. Infectious Disorders: Drug Targets . 2019;19(2):101–104. doi: 10.2174/1871526518666180629134511. PubMed DOI

Bakhtiar N. M., Akbarzadeh A., Casulli A., et al. Therapeutic efficacy of nanocompounds in the treatment of cystic and alveolar echinococcoses: challenges and future prospects. Parasitology Research . 2019;118(9):2455–2466. doi: 10.1007/s00436-019-06416-5. PubMed DOI

Wen H., Vuitton L., Tuxun T., et al. Echinococcosis: Advances in the 21st century. Clinical Microbiology Reviews . 2019;32(2) doi: 10.1128/cmr.00075-18. PubMed DOI PMC

Pensel P. E., Castro S., Allemandi D., Bruni S. S., Palma S. D., Elissondo M. C. Enhanced chemoprophylactic and clinical efficacy of Albendazole formulated as solid dispersions in experimental cystic Echinococcosis. Veterinary Parasitology . 2014;203(1-2):80–86. doi: 10.1016/j.vetpar.2014.01.027. PubMed DOI

Kapan S., Turhan A. N., Kalayci M. U., Alis H., Aygun E. Albendazole is not effective for primary treatment of hepatic hydatid cysts. Journal of Gastrointestinal Surgery . 2008;12(5):867–871. doi: 10.1007/s11605-007-0458-7. PubMed DOI

Lange H., Eggers R., Bircher J. Increased systemic availability of Albendazole when taken with a fatty meal. European Journal of Clinical Pharmacology . 1988;34(3):315–317. doi: 10.1007/bf00540964. PubMed DOI

Vural G., Yardimci M., Kocak M., et al. Efficacy of novel albendazole salt formulations against secondary cystic Echinococcosis in experimentally infected mice. Parasitology . 2020;147(13):1425–1432. doi: 10.1017/s0031182020001225. PubMed DOI PMC

Rigter I. M., Schipper H. G., Koopmans R. P., et al. Relative bioavailability of three newly developed albendazole formulations: a randomized crossover study with healthy volunteers. Antimicrobial Agents and Chemotherapy . 2004;48(3):1051–1054. doi: 10.1128/aac.48.3.1051-1054.2004. PubMed DOI PMC

Albalawi A. E., Alanazi A. D., Baharvand P., Sepahvand M., Mahmoudvand H. High potency of organic and inorganic nanoparticles to treat cystic echinococcosis: an evidence-based review. Nanomaterials . 2020;10(12):p. 2538. doi: 10.3390/nano10122538. PubMed DOI PMC

Nassef N. E., Saad A. G. E., Harba N. M., et al. Evaluation of the therapeutic efficacy of albendazole-loaded silver nanoparticles against Echinococcus granulosus infection in experimental mice. Journal of Parasitic Diseases . 2019;43(4):658–671. doi: 10.1007/s12639-019-01145-z. PubMed DOI PMC

Wen H., New R. R., Muhmut M., et al. Pharmacology and efficacy of liposome-entrapped albendazole in experimental secondary alveolar echinococcosis and effect of co-administration with cimetidine. Parasitology . 1996;113(2):111–121. doi: 10.1017/s003118200006635x. PubMed DOI

Ahmadnia S., Moazeni M., Mohammadi-Samani S., Oryan A. In vivo evaluation of the efficacy of albendazole sulfoxide and albendazole sulfoxide loaded solid lipid nanoparticles against hydatid cyst. Experimental Parasitology . 2013;135(2):314–319. doi: 10.1016/j.exppara.2013.07.017. PubMed DOI

Aminpour S., Rafiei A., Jelowdar A., Kouchak M. Evaluation of the protoscolicidal effects of albendazole and albendazole loaded solid lipid nanoparticles. Iranian Journal of Parasitology . 2019;14(1):127–135. doi: 10.18502/ijpa.v14i1.726. PubMed DOI PMC

Pensel P. E., Ullio Gamboa G., Fabbri J., et al. Cystic echinococcosis therapy: albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice. Acta Tropica . 2015;152:185–194. doi: 10.1016/j.actatropica.2015.09.016. PubMed DOI

Ullio Gamboa G. V., Pensel P. E., Elissondo M. C., et al. Albendazole-lipid nanocapsules: optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus granulosus. Experimental Parasitology . 2019;198:79–86. doi: 10.1016/j.exppara.2019.02.002. PubMed DOI

Darvishi M. M., Moazeni M., Alizadeh M., Abedi M., Tamaddon A. M. Evaluation of the efficacy of albendazole sulfoxide (ABZ-SO)-loaded chitosan-PLGA nanoparticles in the treatment of cystic Echinococcosis in laboratory mice. Parasitology Research . 2020;119(12):4233–4241. doi: 10.1007/s00436-020-06901-2. PubMed DOI

Novoselov K. S., Geim A. K., Morozov S. V., et al. Electric field effect in atomically thin carbon films. Science . 2004;306(5696):666–669. doi: 10.1126/science.1102896. PubMed DOI

Joshi K., Mazumder B., Chattopadhyay P., Bora N. S., Goyary D., Karmakar S. Graphene family of nanomaterials: Reviewing advanced applications in drug delivery and medicine. Current Drug Delivery . 2019;16(3):195–214. doi: 10.2174/1567201815666181031162208. PubMed DOI

Lu N., Wang L., Lv M., Tang Z., Fan C. Graphene-based nanomaterials in biosystems. Nano Research . 2019;12(2):247–264. doi: 10.1007/s12274-018-2209-3. PubMed DOI PMC

Zhao X., Wei Z., Zhao Z., et al. Design and development of graphene oxide nanoparticle/chitosan hybrids showing pH-sensitive surface charge-reversible ability for efficient intracellular Doxorubicin delivery. ACS Applied Materials and Interfaces . 2018;10(7):6608–6617. doi: 10.1021/acsami.7b16910. PubMed DOI

Zhang W., Wang C., Li Z., et al. Unraveling stress-induced toxicity properties of graphene oxide and the underlying mechanism. Advanced Materials . 2012;24(39):5391–5397. doi: 10.1002/adma.201202678. PubMed DOI

Gollavelli G., Ling Y. C. Multi-functional graphene as an in vitro and in vivo imaging probe. Biomaterials . 2012;33(8):2532–2545. doi: 10.1016/j.biomaterials.2011.12.010. PubMed DOI

Li R., Wang Y., Du J., et al. Graphene oxide loaded with tumor-targeted peptide and anti-cancer drugs for cancer target therapy. Scientific Reports . 2021;11(1):p. 1725. doi: 10.1038/s41598-021-81218-3. PubMed DOI PMC

Chen B., Liu M., Zhang L., Huang J., Yao J., Zhang Z. Polyethylenimine-functionalized graphene oxide as an efficient gene delivery vector. Journal of Materials Chemistry . 2011;21(21):7736–7741. doi: 10.1039/c1jm10341e. DOI

Yao C., Tu Y., Ding L., et al. Tumor cell-specific nuclear targeting of functionalized graphene quantum dots in vivo. Bioconjugate Chemistry . 2017;28(10):2608–2619. doi: 10.1021/acs.bioconjchem.7b00466. PubMed DOI

Lu B., Li T., Zhao H., et al. Graphene-based composite materials beneficial to wound healing. Nanoscale . 2012;4(9):2978–2982. doi: 10.1039/c2nr11958g. PubMed DOI

Karahan H. E., Wiraja C., Xu C., et al. Graphene materials in antimicrobial nanomedicine: current status and future perspectives. Advanced Healthcare Materials . 2018;7(13) doi: 10.1002/adhm.201701406.e1701406 PubMed DOI

Sun X., Liu Z., Welsher K., et al. Nano-graphene oxide for cellular imaging and drug delivery. Nano Research . 2008;1(3):203–212. doi: 10.1007/s12274-008-8021-8. PubMed DOI PMC

Ding H., Zhang F., Zhao C., et al. Beyond a carrier: graphene quantum dots as a probe for programmatically monitoring anti-cancer drug delivery, release, and response. ACS Applied Materials and Interfaces . 2017;9(33):27396–27401. doi: 10.1021/acsami.7b08824. PubMed DOI

Pandey H., Parashar V., Parashar R., Prakash R., Ramteke P. W., Pandey A. C. Controlled drug release characteristics and enhanced antibacterial effect of graphene nanosheets containing gentamicin sulfate. Nanoscale . 2011;3(10):4104–4108. doi: 10.1039/c1nr10661a. PubMed DOI

Huang T., Zhang L., Chen H., Gao C. A cross-linking graphene oxide–polyethyleneimine hybrid film containing ciprofloxacin: one-step preparation, controlled drug release and antibacterial performance. Journal of Materials Chemistry B . 2015;3(8):1605–1611. doi: 10.1039/c4tb01896f. PubMed DOI

Matulewicz K., Kaźmierski Ł, Wiśniewski M., et al. Ciprofloxacin and graphene oxide combination-new face of a known drug. Materials . 2020;13(19):p. 4224. doi: 10.3390/ma13194224. PubMed DOI PMC

Wang Y., Zhang D., Bao Q., Wu J., Wan Y. Controlled drug release characteristics and enhanced antibacterial effect of graphene oxide–drug intercalated layered double hydroxide hybrid films. Journal of Materials Chemistry . 2012;22(43):23106–23113. doi: 10.1039/c2jm35144g. DOI

Smyth J., Barrett N. Procedures for testing the viability of human hydatid cysts following surgical removal, especially after chemotherapy. Transactions of the Royal Society of Tropical Medicine and Hygiene . 1980;74(5):649–652. doi: 10.1016/0035-9203(80)90157-1. PubMed DOI

Mohammadzadeh T., Sadjjadi S., Rahimi H., Shams S. Establishment of a modified in vitro cultivation of protoscoleces to adult Echinococcus granulosus; an important way for new investigations on hydatidosis. Iranian Journal of Parasitology . 2012;7(1):59–66. PubMed PMC

Smyth J., Davies Z. In vitro culture of the strobilar stage of Echinococcus granulosus (sheep strain): a review of basic problems and results. International Journal for Parasitology . 1974;4(6):631–644. doi: 10.1016/0020-7519(74)90028-9. PubMed DOI

Smyth J., Miller H. J., Howkins A. Further analysis of the factors controlling strobilization, differentiation, and maturation of Echinococcus granulosus in vitro. Experimental Parasitology . 1967;21(1):31–41. doi: 10.1016/0014-4894(67)90064-1. PubMed DOI

Zou F., Wang X., Han X., et al. Expression and function of tetraspanins and their interacting partners in B cells. Frontiers in Immunology . 2018;9:p. 1606. doi: 10.3389/fimmu.2018.01606. PubMed DOI PMC

Hummers W. S., Offeman R. E., Offeman R. E. Preparation of graphitic oxide. Journal of the American Chemical Society . 1958;80(6):p. 1339. doi: 10.1021/ja01539a017. DOI

Daneshafruz H., Barani H., Sheibani H. Palladium nanoparticles-decorated β-cyclodextrin–cyanoguanidine modified graphene oxide: a heterogeneous nanocatalyst for suzuki–miyaura coupling and reduction of 4-nitrophenol reactions in aqueous media. Journal of Inorganic and Organometallic Polymers and Materials . 2022;32(3):791–802. doi: 10.1007/s10904-021-02218-4. DOI

Si Y., Samulski E. T. Synthesis of water soluble graphene. Nano Letters . 2008;8(6):1679–1682. doi: 10.1021/nl080604h. PubMed DOI

Zhang L., Shi T., Wu S., Zhou H. Sulfonated graphene oxide: the new and effective material for synthesis of polystyrene-based nanocomposites. Colloid and Polymer Science . 2013;291(9):2061–2068. doi: 10.1007/s00396-013-2943-8. DOI

Vinodha G., Shima P., Cindrella L. Mesoporous magnetite nanoparticle-decorated graphene oxide nanosheets for efficient electrochemical detection of hydrazine. Journal of Materials Science . 2019;54(5):4073–4088. doi: 10.1007/s10853-018-3145-z. DOI

Çolak B., Aksoy F., Yavuz S., Emin Demircili M. Investigating the effect of gold nanoparticles on hydatid cyst protoscolices under low-power green laser irradiation. Turkish Journal of Surgery . 2019;35(4):314–320. doi: 10.5578/turkjsurg.4354. PubMed DOI PMC

Norouzi R., Ataei A., Hejazy M., Noreddin A., El Zowalaty M. E. Scolicidal effects of nanoparticles against hydatid cyst protoscolices in vitro. International Journal of Nanomedicine . 2020;15:1095–1100. doi: 10.2147/ijn.s228538. PubMed DOI PMC

Naseri M., Akbarzadeh A., Spotin A., Akbari N. A., Mahami-Oskouei M., Ahmadpour E. Scolicidal and apoptotic activities of albendazole sulfoxide and Albendazole sulfoxide-loaded PLGA-PEG as a novel nanopolymeric particle against Echinococcus granulosus protoscoleces. Parasitology Research . 2016;115(12):4595–4603. doi: 10.1007/s00436-016-5250-8. PubMed DOI