Glycyrrhizin-induced changes in phospholipid dynamics studied by 1H NMR and MD simulation.

Phospholipid bilayer constitutes the basis of the cell membrane. Any changes in its structure and dynamics could significantly affect the properties and functions of the cell membrane and associated proteins. It could, in its turn, affect the mechanism and strength of drug-membrane interaction. Phase transitions in lipid bilayer play an important role in cell life and in transmembrane transport of ions and drug molecules. In the present study we have tried to clarify the mechanism of glycyrrhizin bioactivity by the study of its influence on the lipid dynamics and phase transition of the lipid bilayer. For this purpose, a combination of nuclear magnetic resonance (NMR) and molecular dynamic (MD) simulations was used. Glycyrrhizin is the saponin extracted from licorice root. It displays a wide spectrum of biological activity and is frequently used in traditional medicine since ancient times. Now glycyrrhizin attracts additional attention as a novel multifunctional drug delivery system. We have established that glycyrrhizin interaction with dipalmitoylphosphatidylcholine lipid bilayers leads to changes in lipid mobility and phase transition temperature. NMR and MD results demonstrated that a glycyrrhizin molecule is able to integrate into a lipid bilayer and form stable aggregates inside. We hypothesize that surface curvatures caused by local changes in the lipid composition and the presence of phase boundaries might affect the permeability of the cell membrane.

[Efficacy of a new fenbendazole formulation produced by nanotechnology-based drug delivery system against nematodosis].

The efficacy of a new fenbendazile formulation produced by nanotechnology-based drug delivery system was investigated in45 sheep naturally infected with gastrointestinal nematodes. The formulation showed 95.6% efficacy against Nematodes spp. at a dose of 1.0 mg/kg dw of its active ingredient and 100% efficacy against other species of gastrointestinal nematodes. Given at a dose of 10 mg/kg dw, the basic drug--fenbendazole (substance) displayed 96.39 and 100% efficacy, respectively.

Natural Poly- and Oligosaccharides as Novel Delivery Systems for Plant Protection Compounds.

To increase the bioavailability of plant protection products, we have applied a new approach based on noncovalent association with natural water-soluble polysaccharides and oligosaccharides as delivery systems (DSs). The mechanochemical technique has been applied to prepare the solid-state nanodispersed compositions of antidote 1,8-naphthalic anhydride (NA) with arabinogalactan, sodium salt of carboxymethylcellulose, and glycyrrhizin as DSs. The effect of DSs on the solubility and the penetration of NA into the seeds of barley and wheat has been investigated by various physicochemical techniques. All DSs considerably enhance the solubility of NA and improve its penetration into the grain. The influence of polysaccharides and oligosaccharides on artificial lipid membranes was studied by the NMR relaxation method. It was concluded that the effect of polysaccharides and oligosaccharides on the penetration efficacy of plant protection products might be associated with the detected solubility enhancement and the affinity of DSs to the surface of cell membranes.

Spectroscopic and molecular dynamics characterization of glycyrrhizin membrane-modifying activity.

Glycyrrhizic acid (GA) is a triterpene glycoside extracted from licorice root. Due to its amphiphilicity GA is capable of forming complexes with a variety of hydrophobic molecules, substantially increasing their solubility. GA can enhance the therapeutic effects of various drugs. It was hypothesized that the increased bioavailability of the drug by GA is not only due to increased solubility, but also to enhancement of drug permeability through cell membranes. In this study the interaction of GA with POPC liposomes and model DOPC, POPC and DPPC bilayers was investigated by NMR with addition of shift reagents and MD simulations. This work helps to better understand the mechanism of enhanced drug bioavailability in the presence of GA. NMR and MD reveal that GA does penetrate into the lipid bilayer. NMR shows that GA changes the mobility of lipids. GA is predominantly located in the outer "half-layer" of the liposome and that the middle of the hydrophobic tails is the preferred location. GA freely passes through the bilayer surface to the inner part bringing a few water molecules. Also both approaches indicate pore formation in the presence of GA. The GA interaction with membranes is an additional aspect of the biological activity of GA-based drug delivery systems.

[The effect of the dispersity of tegalid on its bioavailability]. / Vliianie dispersnosti tegalila na ego biodostupnost'.

The impact of the new helminthicide Tegalide, a dibromobenzamide derivative, on its pharmacology was investigated. The agent given as a fine-dispersed form was found to be more intensively absorbed by the body and to be in animals' blood for a longer period of time (MRT fine-dispersed and MVR coarse-dispersed were 88.5 and 50.4 hours, respectively). As the fine-dispersed fraction of Tegalide increased, its bioavailability showed an equivalent increase.