Mikhail V Khvostov1, Sergey A Borisov2, Tatjana G Tolstikova2,3, Alexander V Dushkin4, Biligma D Tsyrenova4, Yulia S Chistyachenko4, Nikolay E Polyakov5, Galina G Dultseva5,3, Andrey A Onischuk5,3, Sergey V An'kov2. 1. Laboratory of Pharmacological Research, N.N. Vorozhtsov Institute of Organic Chemistry SB RAS, 9, Lavrentjeva Prospect, 630090, Novosibirsk, Russia. mihail.hvostov@gmail.com. 2. Laboratory of Pharmacological Research, N.N. Vorozhtsov Institute of Organic Chemistry SB RAS, 9, Lavrentjeva Prospect, 630090, Novosibirsk, Russia. 3. Novosibirsk State University, Novosibirsk, 630090, Russia. 4. Institute of Solid State Chemistry and Mechanochemistry SB RAS, Novosibirsk, 630090, Russia. 5. Voevodsky Institute of Chemical Kinetics and Combustion, SB RAS, Novosibirsk, 630090, Russia.
Abstract
BACKGROUND AND OBJECTIVES: In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen's bioavailability and decrease its effective dose after oral administration. METHODS: The complex with mass ratio as IBU:AG 1:10 was obtained by mechanochemical synthesis and characterized by water solubility, electron microscopy, differential scanning calorimetry, X-ray powder diffraction analysis and 1H-nuclear magnetic resonance spectroscopy. Different animal models of pain and inflammation was used to investigate IBU:AG biological effects. Plasma concentration of IBU and its pharmacokinetic parameters were evaluated after oral introduction. RESULTS: It was found that ibuprofen's effective analgesic and anti-inflammatory dose decreased twofold after its introduction as a complex with AG. The reason of this difference is due to the increase of ibuprofen concentration in rats' plasma: C max of IBU at doses of 20 and 40 mg/kg was found as 0.088 and 0.132 μg/ml, whereas C max of IBU in the complex form was 0.103 and 0.160 μg/ml, respectively. CONCLUSIONS: Thus, we have shown that complexation of the IBU with AG results in its bioavailability increase, reduction of the effective dose and should decrease toxic side effects.
BACKGROUND AND OBJECTIVES: In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen's bioavailability and decrease its effective dose after oral administration. METHODS: The complex with mass ratio as IBU:AG 1:10 was obtained by mechanochemical synthesis and characterized by water solubility, electron microscopy, differential scanning calorimetry, X-ray powder diffraction analysis and 1H-nuclear magnetic resonance spectroscopy. Different animal models of pain and inflammation was used to investigate IBU:AG biological effects. Plasma concentration of IBU and its pharmacokinetic parameters were evaluated after oral introduction. RESULTS: It was found that ibuprofen's effective analgesic and anti-inflammatory dose decreased twofold after its introduction as a complex with AG. The reason of this difference is due to the increase of ibuprofen concentration in rats' plasma: C max of IBU at doses of 20 and 40 mg/kg was found as 0.088 and 0.132 μg/ml, whereas C max of IBU in the complex form was 0.103 and 0.160 μg/ml, respectively. CONCLUSIONS: Thus, we have shown that complexation of the IBU with AG results in its bioavailability increase, reduction of the effective dose and should decrease toxic side effects.
Authors: Yulia S Chistyachenko; Elizaveta S Meteleva; Maria Y Pakharukova; Aleksey V Katokhin; Mikhail V Khvostov; Anastasiya I Varlamova; Igor I Glamazdin; Salavat S Khalikov; Nikolay E Polyakov; Ivan A Arkhipov; Tatyana G Tolstikova; Viatcheslav A Mordvinov; Alexander V Dushkin; Nikolay Z Lyakhov Journal: Curr Drug Deliv Date: 2015 Impact factor: 2.565
Authors: Yulia S Chistyachenko; Alexandr V Dushkin; Nikolay E Polyakov; Mikhail V Khvostov; Tatyana G Tolstikova; Genrikh A Tolstikov; Nikolay Z Lyakhov Journal: Drug Deliv Date: 2014-02-12 Impact factor: 6.419
Authors: Mikhail V Khvostov; Alexander A Chernonosov; Tatjana G Tolstikova; Marat F Kasakin; Olga S Fedorova; Alexander V Dushkin Journal: Biomed Res Int Date: 2013-12-26 Impact factor: 3.411
Authors: Ruiping Kong; Xingyi Zhu; Elizaveta S Meteleva; Nikolay E Polyakov; Mikhail V Khvostov; Dmitry S Baev; Tatjana G Tolstikova; Alexander V Dushkin; Weike Su Journal: Drug Deliv Transl Res Date: 2018-10 Impact factor: 4.617