Inclusion complexes of albendazole (ABZ) with the polysaccharide arabinogalactan from larch wood Larix sibirica and Larix gmelinii were synthesized using a solid-state mechanochemical technology. We investigated physicochemical properties of the synthesized complexes in the solid state and in aqueous solutions as well as their anthelmintic activity against Trichinella spiralis, Hymenolepis nаna, Fasciola hepatica, Opisthorchis felineus, and mixed nematodoses of sheep. Formation of the complexes was demonstrated by means of intrinsic solubility and the NMR relaxation method. The mechanochemically synthesized complexes were more stable in comparison with the complex produced by mixing solutions of the components. The complexes of ABZ showed anthelmintic activity at 10-fold lower doses than did free ABZ. The complexes also showed lower acute toxicity and hepatotoxicity. These results suggest that it is possible to design new drugs on the basis of the ABZ:arabinogalactan complex that are safer and more effective than albendazole.

The purpose of our research was to evaluate the effect of mechanochemical technology on the efficacy of supramolecular complex of fenbendazole (SMCF) with polyvinylpyrrolidone (PVP) polymer against some helminthosis of animals. The SMCF samples with PVP were synthesized using a solid-state mechanochemical technology in activators of impact-abrading type and their physicochemical properties were analyzed. The efficacy of SMCF was studied on the laboratory model of Hymenolepis nana and Trichinella spiralis infection of mice and helminthosis of sheep. In the trials conducted on laboratory models, the supramolecular complex showed 93.94% and 98.56 % efficacy at the dose of 1 mg/kg of body weight (b/w), while the substance of fenbendazole showed 7.97% and 8.33% efficacy at the same dose. A high efficacy (>94%) of the SMCF was revealed at the dose of 2.0 mg/kg of b/w at oral administration against nematodes in naturally infected sheep by the results of the fecal examination, while the substance of fenbendazole was active at the dose of 5.0 mg/kg at single oral administration. Moreover, the SMCF demonstrated 97.37% efficacy at the dose of 2 mg/kg against Moniezia spp. infection of sheep. Physicochemical studies confirmed the increase in solubility of the complex, reducing of particle sizes, amorphization of fenbendazole substance, and incorporating it with micelles of PVP. According to the results, supramolecular complex of fenbendazole with PVP was more active than the basic substance of fenbendazole and its anthelmintic properties were expanded.

A supramolecular complex (SFBZ) of fenbendazole (FBZ) with licorice extract and sodium dioctyl sulfosuccinate is prepared by mechanochemical method, and its anthelminthic activity and metabolism in sheep are studied. Physicochemical studies of SFBZ confirmed its improved solubility and a decrease in the particle size. FBZ and its metabolites are found to display enhanced absorption into the bloodstream. Their maximum concentration in the blood increases by a factor of 2.3–2.5, and the time required to reach this level increases. The efficacy of SFBZ on the laboratory model of Trichinella spiralis infection is 96.27% at a dose of 1 mg/kg a.i. (active ingredient), whereas the efficacy of the FBZ substance administered at the same dose is 13.70%. A single oral dose of 2.0 mg/kg (a.i.) of SFBZ is highly effective against nematodes in naturally infected sheep, as fecal analyses showed; while the FBZ substance revealed 95.97% efficacy at a dose of 5.0 mg/kg. The higher activity of SFBZ is related to its increased solubility and improved absorption in the animal body.

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.