SYNTHESIS OF THE CARBOXYMETHYL CELLULOSE AND N-VINYLIMIDAZOLE GRAFT-COPOLYMERS AND RELEASE INVESTIGATION OF ANTITUMOR DRUG PACLITAXEL FROM THE COPOLYMER ASSOCIATE

Abstract

The goal of this work is synthesis of the sodium salt of carboxymethyl cellulose (Na-CMC) and N-vinylimidazole (VI) graft-copolymers (Na-CMC-g-VI), researching of the interaction between Na-CMC-g-VI and antitumor drug Paclitaxel (Ptx), and release kinetics investigation of the latter from it copolymer associate. Na-CMC-g-VI water-soluble copolymers were obtained by free radical solvent copolymerization in a presence of hydrogen peroxide initiator. The structure of the synthesized copolymers was confirmed by FTIR. Properties of aqueous solutions of the Na-CMC-g-VI copolymers were researched via dynamic light scattering, transmission electron microscopy (TEM), and zeta-measurement. Found that copolymer particles in the solutions are non-spheric macrochain agglomerates with hydrodynamics radii in a range 120-152 nm (Fig.1), and their surface possesses cumulative negative charge. Interaction between Na-CMC-g-VI copolymers and Ptx was researched via UV spectroscopy (Fig. 2), FTIR (Fig. 3-4), and TEM (Fig. 5). Established that associate formation occurs by physical binding by hydrophobic and stacking interactions. In addition, carbonyl groups of Ptx and imidazole cycles of VI grafted chain takes part in the interactions. Ptx release kinetics was researched by in vitro mode in a range of pH values 5.5-6.8 at 38 °C. Changes of the pH values in the described region slightly effect on the release rate (Fig. 6). Different kinetic models were applied to describe the Ptx release process (Fig. 7). Found that Korsmeyer-Peppas kinetic model is the most appropriate model for researching systems, and release process characterized by «non-Fickian» diffusion. To sum up, Na-CMC-g-VI copolymers were synthesized, and their interaction with Ptx in aqueous solutions, as well as release kinetics of the latter from copolymer associate were investigated.

 AKNOWLEDGMENTS

FTIR, TEM, zeta-potential data were obtained with use of equipment of Center of collective usage of scientific equipment of Voronezh State University.