Author/Authors :
ARKHIPOV, Ivan Department of Experimental Therapy - Branch of Federal Scientific Center of Experimental Veterinary Medicine - Russian Academy of Sciences, Moscow, Russia , KHALIKOV, Salavat Department of Physiologically Active Organofluorine Compounds - A.N. Nesmeyanov Institute of Organoelement Compounds - Russian Academy of Sciences, Moscow, Russia , DUSHKIN, Alexander Department of Mechanochemistry of Organic Compounds - Institute of Solid State Chemistry and Mechanochemistry of the Siberian Branch - Russian Academy of Sciences, Novosibirsk, Russia , SADOV, Konstantin Department of Experimental Therapy - Branch of Federal Scientific Center of Experimental Veterinary Medicine - Russian Academy of Sciences, Moscow, Russia , METELEVA, Elizaveta Department of Mechanochemistry of Organic Compounds - Institute of Solid State Chemistry and Mechanochemistry of the Siberian Branch - Russian Academy of Sciences, Novosibirsk, Russia , ARISOV, Michael Department of Experimental Therapy - Branch of Federal Scientific Center of Experimental Veterinary Medicine - Russian Academy of Sciences, Moscow, Russia , VARLAMOVA, Anastasiya Department of Experimental Therapy - Branch of Federal Scientific Center of Experimental Veterinary Medicine - Russian Academy of Sciences, Moscow, Russia
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.
Keywords :
Efficacy , Praziquantel , Supramolecular complex , Mechanochemistry , Disodium salt of glycyrrhizic acid
