Contents lists available at ScienceDirect Veterinary Parasitology journal homepage: www.elsevier.com/locate/vetpar Research paper The efficacy of the supramolecular complexes of niclosamide obtained by mechanochemical technology and targeted delivery against cestode infection of animals Ivan A. Arkhipov a , Konstantin M. Sadov b , Yulia V. Limova b , Alexandra K. Sadova b , Anastasiya I. Varlamova a, ⁎ , Salavat S. Khalikov c , Alexandr V. Dushkin d , Yulia S. Chistyachenko d a All-Russian Scientific Research Institute of Fundamental and Applied Parasitology of Animals and Plants named after K.I. Skryabin, Bolshaya Cheremushkinskaya street 28, 117218 Moscow, Russia b Scientific Research Veterinary Station of the Russian Academy of Agricultural Sciences, Magnitogorskaya street 8, 446013 Samara, Russia c A.N. Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences, Vavilova street 28, 119991 Moscow, Russia d Institute of Solid State Chemistry and Mechanochemistry of the Siberian Branch of the Russian Academy of Sciences, 630128, Novosibirsk, Kutateladze str., 18, Russia ARTICLE INFO Keywords: Efficacy Niclosamide Supramolecular complexes Polyvinylpyrrolidone polymer ABSTRACT Niclosamide is an anthelmintic that is widely used to treat cestode infection of animals. The efficacy of the supramolecular complexes of niclosamide obtained by mechanochemical technology and targeted delivery was studied in hymenolepiosis of mice and monieziosis of sheep. The efficacy of new substances of niclosamide with polyvinylpyrrolidone polymer in different ratios (1:10; 1:5; 1:2) was determined by the results of helmintho- logical necropsy of the small intestine of sheep and mice. Pre-treatment eggs per gram (EPG) were not sig- nificantly different (P > 0.1) among groups. The controlled test was used to evaluate the efficacy. A high efficacy (> 95% efficacy) of the supramolecular complexes of niclosamide with PVP (SCoNwPVP) was shown in different ratios (1:10; 1:5 and 1:2) at a dose of 20 mg/kg of body weight at oral administration against Hymenolepis nana in mice and Moniezia expansa in sheep. Whereas the basic drug - substance of niclosamide was effective at a dose of 100 mg/kg of b/w. No adverse effects of the drugs on animal health were detected during the study. 1. Introduction Cestodoses of animals are widespread and prevalence of infection of animals ranges from 60 to 100% in some regions of the Russian Federation (Akbayev, 1983; Magomedov, 2000; Belova, 2011). Ano- plocephalatosis and especially monieziosis of animals cause significant losses of production because of high prevalence and mortality of young infected animals (Tsoloev, 1999; Chetvertnov et al., 2009). Lambs are more susceptible and massive infections can cause diarrhea, reduced weight gain and intestinal obstruction. It was determined that the body weight gain of the infected lamb is 1.62 times less than the body weight of a healthy animal when calculating the economic damage in mon- ieziosis of sheep. Infection with Moniezia expansa was associated with reduced weight gain estimated at 4.16 kg, with reduced wool yield estimated at 0.42 kg and mortality was 7.1% per animal (Safiullin, 1997). Niclosamide (syn.: 5-Chloro-N-(2-chloro-4-nitrophenyl)-2 hydro- xybenzamide, monsonil, fenasal, yomezan) is a chlorinated salicylanilide anthelmintic that is used to treat tapeworm infection in a wide range of animals (Reynolds, 1989). Niclosamide is also used against aquatic vertebrates and crustaceans (Goldsmith, 1984). It is a white to yellowish odorless crystalline powder; melting point 224 °C; practically insoluble in water; sparingly soluble in ether, ethanol, chloroform, and soluble in acetone; it is routinely administered orally to pets and livestock. The commercially available ethanolamine salt dis- solves in distilled water (The Merck Index, 2001). The mode of pharmacological action of niclosamide is associated with uncoupling of oxidative phosphorylation or stimulation of ATPase activity (Weinbach and Garbus, 1969). Niclosamide is used to treat cestodosis of sheep, goats and cattle (monieziosis, avitellinosis, thysa- nieziosis) at a dose of 100 mg/kg. It is also used at the same dose against anoplocephalatosis of horses, dipylidiosis and other taeniosis of carnivores. Side effects are infrequent, mild and transitory. Adverse events include nausea, vomiting, diarrhea, and abdominal pain (Campbell and Rew, 1986). In addition niclosamide is an anticancer and protonophric agent. It http://dx.doi.org/10.1016/j.vetpar.2017.08.019 Received 21 April 2017; Received in revised form 24 August 2017; Accepted 28 August 2017 ⁎ Corresponding author. E-mail address: arsphoeb@mail.ru (A.I. Varlamova). Veterinary Parasitology 246 (2017) 25–29 0304-4017/ © 2017 Elsevier B.V. All rights reserved. MARK