Synthesis and Characterization of Phosphorylcholine-based Polymers and Nanogels via the Reversible Addition Fragmentation Chain Transfer Process.

摘要

2-Methacryloyloxyethyl Phosphorylcholine is an interesting biocompatible monomer. An improved method for the synthesis of poly(MPC) and its copolymers using Reversible Addition-Fragmentation chain Transfer (RAFT) has been discussed in the first part of the thesis. Previous reports related to the synthesis of MPC homopolymers and copolymers in aqueous medium are found to be less effective because of the hydrolysis of chain transfer agent in water. Hydrolysis of chain transfer agent results in the loss of active chain ends thereby, reducing control over polymerization and increasing the polydispersity of resulting polymers. Therefore, in this work MPC polymers were synthesized by RAFT using methanol as solvent. This method of synthesis produced polymers having controlled molecular weights as well as narrow polydispersities. Di-block and random copolymers of MPC were also synthesized using cationic monomers like 2- aminoethyl methacrylamide hydrochloride (AEMA) and 2-aminopropyl methacrylamide hydrochloride (APMA) and carbohydrate monomers 2-gluconamidoethyl methacrylamide (GAEMA) and 2-lactobionamidoethyl methacrylamide (LAEMA) in various feed ratios. The polymers obtained were well defined and showed polydispersity values close to one.;In the second part of the work, methoxydiethylene glycol methacrylate (MeODEGM)-MPC based thermo-responsive core-shell nanogels were synthesized for use in protein encapsulation and release. The size of the nanogels was controlled by varying the concentration of cross-linker. The nanogels were synthesized using an acid degradable cross-linker which helped in the release of encapsulated protein at acidic pH. The effect of various parameters on encapsulation efficiency of proteins was studied and it was found that apart from the size of protein, the cross-linker concentration of nanogel also affected the amount of protein encapsulated. AEMA, which was used as a co-monomer in the core, imparted a cationic charge to the nanogel core and hence helped in the encapsulation of oppositely charged proteins. The study of the release profiles of the nanogels at low pH revealed a controlled release scenario.