Session Speaker

Synergy of Drug Transport and Efficacy: Drugs Bound to Glycyrrhizin
Tatyana Victorovna Leshina
Russia

This work was done in an attempt to solve a problem of the improving of the properties of drugs by using their complexes with Nanosized Supramolecular Compounds. Complexes of several drugs (Nifedipine, Lappaconitin, Simvastatin, Atorvastatin) and biologically active Carotenoids with pharmaceutically acceptable complex-forming Glycyrrhizic Acid (GA) are investigated by means of modern physical methods (NMR, UV spectroscopy, CIDNP, Solution Small-Angle X-Ray Scattering). NMR and UV spectroscopy and animal studies were used to explore the regularities of complexing between calcium channel blocker Nifedipine (NF) and glycyrrhizin and the influence of GA on the therapeutic activity of NF. 1H NMR and UV-VIS spectra have produced illustrative evidence that NF forms stable complexes with GA.

In the preclinical study of the activity of NF-GA complexes which employed the model of CaCl2 induced arrhythmia in rats, it has been shown that minimum therapeutic dose of NF in the complex with GA is 300 times lower than that of free NF. Animal studies have also demonstrated the increase in hypotensive activity of the NF-GA complex which allowed for 9.6-fold decrease of the active substance content with retaining of the required therapeutic activity. The formation of complexes GA with antiarrhythmic drug Lappaconitin (Lap) was observed using UV spectroscopy and it was shown that minimum therapeutic dose of Lap in the complex with GA needed to relieve arrhythmia in rats is decreased in 10 times as compared to free Lap. Complexation of GA and antihyperlipidemic drugs -statins (Simvastatin, Atorvastatin) with stoichiometric ratio 4: 1 was observed by means of NMR and UV spectroscopy.

In particular, it was shown that complex of Simvastatin with GA inhibits 3-HMG-CoA -reductase according to uncompetitive mechanism while free Simvastatin demonstrate competitive inhibition. Supramolecular complexes of carotenoids are of keen interest due to their antioxidant properties attract the attention of physicians and pharmacists.

Our investigation of supramolecular inclusion complexes of set of carotenoids with glycyrrhizin have shown that the complexation has a substantial effect on the reactivity of carotenoids, specifically antioxidant activity, and stability. This work was supported by the grant 08-03-00372 of Russian Foundation of Basic Research.