ATRP SYNTHESIS AND SELF-ASSEMBLY BEHAVIOR OF CHITOSAN-O-PMPEGMA

The bromized sodium dodecyl sulfate (SDS)-chitosan (CS) complex (Br-SCC) was synthesized by conjugating 2-bromo-2-methyl propionic acid to the hydroxyl groups of SCC which was used as an organo-soluble precursor in this study. Br-SCC was used as a macromolecular ATRP initiator to polymerize methyl ether poly(ethylene glycol) methacrylate (PMPEGMA) using copper (I) bromide/bipyridine as a catalyst, yielding SCC-O-PMPEGMA. SDS was removed from the product by precipitating SCC-O-PMPEGMA solution into aqueous tris(hydroxymethyl) amine (Tris) medium. The chemical structure of the intermediate and CS-O-PMPEGMA was studied by FTIR and H-1-NMR. The substitution degree of bromobutyric acid could be modulated by bromobutyric acid/SCC feed ratio. The degree of polymerization of PMPEGMA could be controlled by varying the PMPEGMA/Br-SCC ratio. Complexation behaviors between CS-O-PMPEGMA and heparin were studied by dynamic light scattering, zeta potential analyzer and TEM. With the increase of heparin/CS molar ratio (X), there was an increase in the nanoparticle size and decrease in the zeta potential of the particles. When X was above 2, the size and the zeta potential reached a plateau stage. The ultimate size of the spherical nanoparticles was about 44 nm and the zeta potential was -8.9 mV. CS-O-PMPEGMA which could be conveniently synthesized according to the scheme proposed in this study has well-defined chemical structure. The grafting of PMPEGMA has no effect on the cationic density of the final product. In addition, the copolymers could form spherical micelles with anionic agents. The above characteristics of CS-O-PMPEGMA make it promising for tumor targeting and gene delivery.