Original Article

Anthelmintic Efficacy of Supramolecular Complex of Praziquantel Obtained by Mechanochemical Technology

Abstract

Background: A supramolecular complex of praziquantel (PZQ) with disodium salt of glycyrrhizic acid (Na2GA) was obtained by mechanochemical technology to increase solubility, absorption rate and hence bioavailability of the drug and reduction its therapeutic doses. The aim of our study was evaluation of anthelmintic efficacy of supramolecular complex of PZQ.

Methods: Different samples of PZQ with Na2GA were obtained by mechanochemical processing and examined for some physico-chemical properties. The anthelmintic activity of the most perspective samples was studied on the laboratory model of Hymenolepis nana infection of mice and Moniezia expansa infection of sheep by the results of helminthological necropsy of the small intestines (the controlled test).

Results: A high efficacy (> 98%) of supramolecular complex of PZQ with Na2GA (1/10) was shown at doses of 3; 2 and 1 mg/kg of body weight at single oral administration against H. nana in mice and M. expansa in sheep. While the basic PZQ had 27.19% and 36.64% efficacy respectively at the dose of 1 mg/kg. The PZQ:Na2GA 1/10 physical mixture (without mechanochemical processing) revealed no anthelmintic efficacy.

Conclusion: Joint mechanochemical treatment the PZQ substance and Na2GA led to increased solubility, reduction of particle sizes, amorphization of substance, incorporating it with micelles of glycyrrhizic acid and high anthelmintic efficacy in reduced dose. The supramolecular complex of praziquantel was found to be a perspective anthelminthic with enhanced pharmacological activity that needs further research.

1. Sergiev VP. Atlas of clinical parasitology and tropical medicine. Moscow: Author's Academy; 2010.
2. Campbell WC, Rew RS. Chemotherapy of parasitic diseases. New York and London: Plenum Press; 1986.
3. Thomas H, Gönnert R, Pohlke R, et al. A new compound against adult tapeworms. Thessoloniki: Proc of the 7th Int Conf of the World Ass for the Advancement of Vet Parasitol; 1975.
4. Andrews P, Thomas H, Pohlke R, et al. Praziquan-tel. Med Res Rev. 1983; 3(2):147-200.
5. Riviere JE, Papich MG. Veterinary pharmacology & Therapeutics. 9th ed. Hoboken: Willey Blackwell; 2009.
6. Graebin CS, Merillon JM, Ramawat K. The phar-macological activities of glycyrrhizinic acid (“glycyr-rhizin”) and glycyrrhetinic acid. In: editors. Sweet-eners. Nature Public Health Emergency Collectio. 2017. p. 245-261.
7. Dushkin AV, Tolstikova TG, Khvostov MV, et al. Complexes of polysaccharides and glycyrrhizic acid with drug molecules. Mechanochemical synthesis and pharmacological activity. In: Karunaratn DN, editor. The complex world of polysaccharides. Ri-jeka: InTech; 2012. p. 573–602.
8. Habriev RU. The guidance to experimental (pre-clinical) studying of new pharmacological substanc-es. Moscow: Publishing House Medicine; 2005.
9. The order of the Ministry of Health of the Russian Federation, April 1st, 2016, No. 200. On the ap-proval of the rules of good clinical practice.
10. European Convention for the Protection of Verte-brate Animals used for experimental and other sci-entific purposes. Strasbourg, 1986.
11. Meteleva ES, Chistyachenko YS, Suntsova LP, et al. Physicochemical properties and anti-opisthorchosis effect of mechanochemically synthesized solid compositions of praziquantel with glycyrrhizic acid disodium salt. Dokl Biochem Biophys. 2018; 481:228-31.
12. Zhang Q, Polyakov NE, Chistyachenko YS, et al. Preparation of curcumin self-micelle solid disper-sion with enhanced bioavailability and cytotoxic ac-tivity by mechanochemistry. Drug Deliv. 2018; 25(1):198-209.
13. Higuchi TA, Connors KA. Phase solubility tech-niques. In: Reilley CN, editor. Advances in Analyti-cal Chemistry and Instrumentation. New York: Wiley-Interscience; 1965. p. 117-212.
14. Kansy M, Senner F, Gubernator K. Physicochemi-cal high throughput screening: parallel artificial membrane permeation assay in the description of passive absorption processes. J Med Chem. 1998; 41(7):1007-10.
15. Khalikov SS, Chistyachenko YS, Dushkin AV, et al. Development of anthelmintic drugs of increased efficiency on the basis of intermolecular complexes of active substances with water-soluble polymers including polysaccharides. J Chem Sustain Dev. 2015; 5:567-77.
16. Arkhipov IA, Sadov KM, Limova YV, et al. The efficacy of the supramolecular complexes of ni-closamide obtained by mechanochemical technolo-gy and targeted delivery against cestode infection of animals. Vet Parasitol. 2017; 246:25-9.
17. Arkhipov IA, Engasheva ES, Khalikov SS, et al. Innovative technology for preparing of anthelmintic drugs. Veterinary. 2016; 12:3-10.
18. The order of the Ministry of Health of the USSR, October 10th, 1983, No. 1179 “On approval of feed standards for laboratory animals in health facilities”.
19. Astafyev BA, Yarotsky LS, Lebedeva MN. Exper-imental models of parasites in biology and medicine. Moscow: Nauka; 1989.
20. Kalashnikov AP, Fisin VF, Shcheglova VV, et al. Norms and rations of feeding livestock. Moscow: Rosselkhozakademiya; 2003.
21. Ministry of Agriculture, Fisheries and Food. Manual of veterinary parasitological laboratory techniques. Reference Book 418. London: Her Majesty’s Sta-tionery Office; 1986.
22. Wood IB, Amaral NK, Bairden K, et al. World Association for the Advancement of Veterinary Parasitology (WAAVP) second edition of guidelines for evaluating the efficacy of anthelmintics in rumi-nants (bovine, ovine, caprine). Vet Parasitol. 1995; 58(3):181-213.
23. Ivashkin VM, Oripov AO, Sonin MD. The deter-minant of helminthes of small cattle. Moscow: Nauka; 1989.
24. Arkhipov IA. Anthelmintics: pharmacology and application. Moscow: Rosselkhozakademiya; 2009.
25. Linderberg M, Kopp S, Dressman JB. Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines ac-cording to the biopharmaceutics classification sys-tem. Eur J Pharm Biopharm. 2004; 58(2):265-78.
26. Dayan AD. Albendazole, mebendazole and pra-ziquantel. Review of non-clinical toxicity and phar-macokinetics. Acta Trop. 2003; 86(2-3):141-59.
27. Skira VN, Dushkin AV, Chistyachenko YS, et al. Efficacy of the supramolecular complex of fen-bendazole in nematodiasis of sheep. Rus Parasitol J. 2016; 76-81.
28. Kong R, Zhu X, Meteleva ES, et al. Enhanced solubility and bioavailability of simvastatin mecha-nochemically obtained complexes. Int J Pharm. 2017; 534(1-2):108-118.
29. Selyutina OY, Apanasenko IE, Polyakov NE. Membrane-modifying activity of glycyrrhizic acid. Russ Chem Bull. 2015; 64:1555-1559.
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IssueVol 15 No 3 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijpa.v15i3.4201
Keywords
Efficacy Praziquantel Supramolecular com-plex Mechanochemistry Disodium salt of glycyrrhizic acid
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How to Cite
1.
ARKHIPOV I, KHALIKOV S, DUSHKIN A, SADOV K, METELEVA E, ARISOV M, VARLAMOVA A. Anthelmintic Efficacy of Supramolecular Complex of Praziquantel Obtained by Mechanochemical Technology. Iran J Parasitol. 2020;15(3):364-373.