Title : Physicochemical and biophysical study of mechanisms the drugs bioavailability enhancement with new multifunctional delivery systems
One of the most important problems of modern pharmaceutics is the low solubility and bioavailability of drug compounds. These problems are solved by using various delivery systems that can form water-soluble “guest-host” complexes with drug molecules. One of the advantages of this approach is a significant reduction in therapeutic dose, as well as a reduction in side effects, which is especially important, for example, in the case of highly toxic anticancer drugs. In our work we focus our attention on oligosaccharides and polysaccharides which are able to form water soluble inclusion complexes with various lipophilic drugs. The examples of such carriers are polysaccharide arabinogalactan (AG), saponin glycyrrhizic acid (GA) and oligosaccharide cyclodextrin.
The report will illustrate the use of various physical methods, primarily nuclear magnetic resonance, to study the inclusion complexes of a wide range of drugs, as well as the effect of drug carriers on the physical and functional properties of cell membranes. In particular, the ability of GA to integrate into the lipid bilayer and its effect on the lipid mobility in the membrane was studied by NMR relaxation and molecular dynamics techniques. The use of these methods made it possible to establish that GA molecule is embedded in the outer half-layer of the membrane and has a significant effect on the mobility of phospholipids in the bilayer. The permeability enhancement by GA and AG carriers for model membrane as well as for erythrocyte cells and myeloid leukemia K562 cells has been demonstrated by PAMPA and NMR techniques. This comprehensive study sheds some light on the mechanism of the drugs bioavailability enhancement in the presence of glycyrrhizin and arabinogalactan and offers the new possibilities of their use as drug carriers. Several examples of the influence of complexation on the drugs stability and reactivity will be presented. In conclusion some evident advantages of mechanochemical technique for development of novel drug formulations will be discussed. This work was supported by Russian Scientific Foundation, grant No. 18-13-00047 and the Russian Foundation for Basic Research, grant No. 18-416-540007.
Audience take away:
• New data on the molecular mechanisms of drug delivery by novel natural drug carriers will be interesting to wide audience of scientific researcher in the fields of medicinal chemistry, supramolecular chemistry and membrane biophysics, as well as for education purposes.
• From practical point of view, our experience in this field and new technologies developed in our labs can be helpful for design and development of new drug formulations with predictable properties.