Drug Discovery and Targeting (Track)

Water soluble drugs conjugates with oligo- and polysaccharides. New approach for drug design and delivery

Nikolay E. Polyakov
Institute of Chemical Kinetics and Combustion, Novosibirsk, 630090, Russia


Abstract:

We present a new approach for preparation of water soluble drug conjugates with natural oligosaccharides polysaccharides using mechano-chemical technique. Inclusion complexes of a series of insoluble drugs and carotenoids with b-glycyrrhizic acid (GA) and natural polysaccharide arabinogalactan (AG) exhibit not only enhanced water solubility, but also enhanced stability and activity. Both GA and AG are of considerable interest to pharmacologists because of their unique physiological activity. Also, there are no rigorous restrictions on the size of a “guest” molecule in contrast to widely used cyclodextrin complexes. We have demonstrated that application of glycyrrhizic acid strengthens the therapeutic efficiency of some hypotensive and anti-arrhythmic drugs by orders of magnitude and reduces side effects. The complex of simvastatin with GA shows not only enhanced activity, but also changes the mechanism of enzyme inhibition. In the present work we report the first example of water soluble carotenoid complexes. It was demonstrated that incorporation of carotenoids into arabinogalactan macromolecule results in significant increase their solubility in water and stability. On the other hand, inclusion complexes of some carotenoids with GA show enhanced ability (in orders of magnitude) to scavenge free radicals. We propose also that GA and AG conjugates might be used for targeted drug delivery to cancer cells and photodynamic therapy.

The financial support of Russian Foundation for Basic Research, grant 08-03-00372 and the U.S. Department of Energy, Grant DE-FG02-86ER13465 are gratefully acknowledged.

Keywords: drug delivery, drug solubility, inclusion complexes, glycyrrhizic acid, arabinogalactan, polysaccharides, carotenoids.