Kinetic Of The SET-LRP Synthesis Of Oligo(Ethylene Glycol) Methacrylate And Its Derivatives In The Application Of Drug Release

Chitosan-O-poly(oligo(ethylene glycol) methacrylate) (CS-O-POEGMA) was synthesized through single electron transfer-living radical polymerization (SET-LRP) of OEGMA, using O-brominated chitosan (CS-Br) as an initiator and Cu(I)Br as the catalyst. The polymerization kinetics under different conditions was studied using in situ 1H-NMR. It was found that with the decrease of medium pH there was an associated decrease in the polymerization rate. This could be attributed to the fact that the protonation of the ligand at low pH could impair its coordination ability towards copper. When CS-Br concentration was raised to a certain extent, gelation took place during polymerization. The degree of substitution of bromobutyrate groups in CS-Br had little effect on the polymerization kinetics in pH 5.0 buffer solution, suggesting the conformation of chitosan backbone was in an extended state at pH 5.0.Then the amino group of the CS-O-POEGMA was chloracetylated by using citraconic anhydride(CTA) to get its derivatives CS-O-POEGMA-CTA. Doxorubicine(Dox), a model hydrophobic chemotherapeutic agent, were used to form micelles by dialysis method in buffer solution. The load and release behavior and the cycotoxicity towards HepG2 cells of these CS-POEGMA-CTA-Dox micelles were studied. It was found that CS-O-POEGMA-CTA and Dox could form micelles spontaneously in buffer solution through electrostatic interaction and intermolecular hydrogen-bond interaction. It was also found that the release behaviors of Dox in vitro were strongly dependent of the medium pH. The amount of Dox released from these CS-POEGMA-CTA-Dox micelles in pH 7.4 PBS was a little, indicating these micelles could be stable in the circulation process as well as protect the drugs loaded. When in low pH acid tumor microenvironment, these micelles dissociated, leading to a large release of the contained drugs. The cytotoxicity of CS-POEGMA-CTA-Dox micelles was evaluated using HepG2 cells as model. It was revealed that the cytotoxicity of these blank micelles could be tolerable for normal tissues while the CS-POEGMA-CTA-Dox micelles showed a strong cytotoxicity.