A Novel Polymeric Prodrugs Synthesized by Mechanochemical Solid-State Copolymerization of Glucose-Based Polysaccharides and Vinyl Monomers

We developed the novel polymeric prodrugs synthesized by mechanochemical solid-state copolymerization of glucose-based polysaccharides (dextran orglycogen) and the methacryloyloxy derivative of 5-fluorouracil (5-FU). The copolymerization proceededreadily and each polymeric prodrug was quantitatively obtained within8 h reaction. The number average molecular weight (Mn) and polydispersity (H) of the polymeric prodrug synthesized from dextran was 24,000 g/mol and 5.10, respectively. The number average particle diameter of the polymeric prodrug derived from glycogen was 14.9 nm. The hydrolysis profiles of the polymeric prodrug synthesized from dextranapparently followed the first-order kinetics, and 100% drug release was observed under the experimental condition used. The polymeric prodrug derived from glycogen also continued to release 5-FU at the first-order rate up to 5 h, followed by its rate constant decreased gradually. These results suggest that lower accessibility of water molecules for the synthetic polymer chains inside the glycogen particle might cause the gradual decrease of drug release rate.