Original Article

Synthesis and Clinical Examination of Novel Formulations of Ivermectin, Albendazole and Niclosamide for the Treatment of Equine Gastrointestinal Helminthoses

Abstract

Background: This study aimed to develop new complex preparations of ivermectin, niclosamide and albendazole based on solid-phase mechanochemical technology, and to evaluate their efficacy against equine nematodosis and cestodosis.

Methods: Novel formulation of antiparasitic paste were prepared using joint mechanochemical treatment of ivermectin (0.2 mg/kg bodyweight; BW), niclosamide (10 mg/kg BW) and albendazole (3, 5, 10 mg/kg BW) substances with polyvinylpyrrolidone and arabinogalactan. For the evaluation of activity of different doses of formulations against gastrointestinal tract helminths a total of 151 adult horses of the Novoaltai breed weighing 450–500 kg naturally infected with strongyles (>150 egg per gram of faeces, EPG), Parascaris spp. (>20 EPG) and Anoplocephala spp. (>10 EPG) were selected. Antiparasitic pastes were orally fed to the horses and faecal egg count reduction counts were compared prior to and 14 days after the treatment.

Results: Pastes with mechanically modified ivermectin showed 91.4–100% efficacy against strongyles and Parascaris. Pastes with modified albendazole and niclosamide were also effective against Anoplocephala in all tested dosages i.e. 78.6–100%. In particular, treatment with two formulations containing i) 0.2 mg ivermectin, 10 mg albendazole, 10 mg niclosamide, and ii) 0.2 mg ivermectin, 3 mg albendazole showed 100% efficacy against strongyles, Parascaris and Anoplocephala.

Conclusion: Solid-phase mechanochemical technology could be applied in equine anthelminthics production. It is suggested that future studies focus on plasma concentration-time profile of these highly effective pastes.

1. Sazmand A, Bahari A, Papi S, Otranto D. Parasitic diseases of equids in Iran (1931–2020): a literature review. Parasites Vectors. 2020;13:586.
2. Nielsen MK, Reinemeyer CR. Handbook of equine parasite control. Second ed. NJ: Wiley Online Library; 2018.
3. Efremova EA, Marchenko VA, Smertina MA. Parascariasis of horses in the conditions of Central Altai. Theory Pract Parasit Dis Control. 2021;22:187–92.
4. Efremova EA, Marchenko VA. Epizootic aspects of helminthiases in horses in the Altai Republic. Proc VIth Int Res Pract Conf. 2017;216-8.
5. Marchenko VA, Efremova EA. Epizootic situation of helminthiasis of farm animals in the Altai Republic. Theory Pract Parasit Dis Control. 2019;20:341–6.
6. Arkhipov IA. Anthelminthics: Pharmacol-ogy and application. Moscow; 2009.
7. Vercruysse J. Macrocyclic Lactones in An-tiparasitic Therapy. USA: CABI; 2002.
8. Pandit S, Ghosh JD, Chinya A, et al. Eval-uation of anthelmintic efficacy of ivermec-tin, levamisole and albendazole against naturally occurring gastrointestinal nema-todosis in Garole sheep. J Vet Parasitol. 2009;23:121-5.
9. Marchenko VA, Khalikov SS, Vasilenko YA, et al. Innovative anthelmintic based on mechanochemical technology and their efficacy against parasitic infection of sheeps. J Adv Vet Anim Res. 2020;7(4):8718–25.
10. Marchenko VA, Khalikov SS, Efremova EA, et al. Efficiency of novel formulations of ivermectin and albendazole in parasitic infections of sheep in the Altai Mountains of Russia. Iran J Parasitol. 2021;16(2):198-208.
11. Mucalo MR, Bullen CR, Manley-Harris M, et al. Arabinogalactan from the Western larch tree: a new, purified and highly water-soluble polysaccharide-based protecting agent for maintaining precious metal nanoparticles in colloidal suspensions. J Mater Sci. 2002;37 (3):493–504.
12. Pitkänen L, Heinonen M, Mikkonen KS. Safety considerations of plant polysaccharides for food use: a case study on phenolic-rich softwood galactoglucomannan extract. Food Funct. 2018,9:1931-43.
13. Ma BL, Yang Y, Dai Y, et al. Polyethylene glycol 400 (PEG400) affects the systemic exposure of oral drugs based on multiple mechanisms: taking berberine as an example. RSC Adv. 2017;7:2435–42.
14. Khalikov SS, Dushkin AV. Strategies for solubility enhancement of anthelmintics. Pharm Chem J. 2020;54(5):504-8.
15. Khalikov SS, Lokshin BV, Ilyin MM. Solid dispersions of medamine and albendazole with water-soluble polymers: preparation and properties. Pharm Chem J. 2020;54(8):816-21.
16. Manual of Veterinary Parasitological La-boratory Techniques. Ministry of Agricul-ture, Fisheries and Food, UK; 1986.
17. European Convention for the Protection of Vertebrate Animals used for Experi-mental and Other Scientific Purposes. Strasbourg; 1986.
18. Kondrakhin IP, Arkhipov AV, Levchenko VI. Methods of veterinary clinical laborato-ry diagnostics. Moscow; 2004.
19. Santos DW, de Carvalho LMM, Molento MB. Identification of third stage larval types of cyathostomins of equids: An im-proved perspective. Vet Parasitol. 2018;260:49-52.
20. Khabriev RU. Guidelines for the experi-mental (preclinical) study of new pharma-cological substances. Moscow; 2005.
21. Wood IB, Amaral NK, Bairden K, et al. World Association for the Advancement of
Veterinary Parasitology (W.A.A.V.P.) sec-ond edition of guidelines for evaluating the efficacy of anthelmintics in ruminants (bo-vine, ovine, caprine). Vet Parasitol. 1995;58(3):181-213.
22. Kalashnikov AP, Fisin VF, Shcheglova VV. Norms and diets of livestock feeding. Moscow; 2003.
23. Arkhipov IA, Sadov KM, Limova YV, et al. The efficacy of the supramolecular complexes of niclosamide obtained by mechano-chemical technology and targeted elivery against cestode infection of animals. Vet Parasitol. 2017;246:25–9.
24. Varlamova AI, Kotchetkov PP, Arkhipov IA, et al. Pharmacokinetic profile, tissue residue depletion and anthelmintic efficacy of supramolecular fenbendazole. Int J Pharm. 2021;607:120957.
25. Marchenko VA, Khalikov SS. Supramolec-ular complexes of drugs for parasitic sheep invasions. IOP Conf Ser Earth En-viron Sci. 2020;548:082006.
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IssueVol 18 No 1 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijpa.v18i1.12381
Keywords
Albendazole Helminths Horses Ivermectin Mechanochemistry Niclosamide
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How to Cite
1.
Marchenko V, Khalikov S, Biryukov I, Efremova E, Ilyin M, Sazmand A. Synthesis and Clinical Examination of Novel Formulations of Ivermectin, Albendazole and Niclosamide for the Treatment of Equine Gastrointestinal Helminthoses. Iran J Parasitol. 2023;18(1):66-75.