Synthesis And Properties Of Stimuli-responsive Chitosan Graft Copolymers

Chitosan has recently been extensively used in the field of biomaterial and biomedicine because of its nontoxicity, good biocompatibility, and biodegradability properties. Due to the structure of chitosan, there are many functional groups which can be modified with stimuli-sensitive polymer chains. Chitosan based graft copolymer would possess new properties with minimum loss of the initial properties of chitosan. Based on the relationship between the structure and properties of polymer chains, it is feasible to designed and synthesize special chitosan graft copolymer, which will be of great importance in the chitosan research.In this dissertation, two kinds of chitosan graft copolymer were synthesized with "living"/controlled polymerizations. The main work done shows as follows:1. For the development of biocompatible and degradable biomaterials, a kind of well-defined graft copolymer consisting of chitosan back-bone and amphiphilic PEO-PLLA-PEO branch chains was synthesized by Cu(0) catalyzed one-pot strategy combining "click" chemistry and single electron transfer-nitroxide radical coupling (SET-NRC) reaction. First, the precursor of6-azide-N-phthaloyl-chitosan was prepared via a series of the modification of original chitosan, such as phthaloylation, tosylation, and azidation. Furthermore, TEMPO-PEO-alkyne and PEO-PLLA-Br were designed and produced via sequential ring-opening polymerization and substitution of hydroxyl-terminated group. Then, the one-pot coupling reactions between these precursors were performed in the presence of nanosized Cu and PMDETA. All the intermediates and target products were characterized through1H NMR, FTIR, ESR, and DSC.2. N-chitosan-g-(PEO-PLLA-PEO) could assemble to micelle in aqueous solution. The micellization process was divided into two phases through the fluorescence measurement using pyrene as fluorescent probe. The micellar size firstly decreased and then increase with the temperature increasing. Moreover, the phenomenon was more obvious with the lower EO/LA value of branch chains. The graft copolymer solution was easier to form hydrogel than that of mPEO-PLLA-mPEO solution, which gel-sol transition temperature could be modulated by the EO/LA and solution concentration. Indomethacin was chosen as a model drug to assess that the graft copolymer can be used as a drug carrier.3. In order to develop stimuli-responsive hydrogel, chitosan graft copolymer with chitosan back-bone and PNIPAAM-b-PAA branch chains was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization in DMF. The chain transfer agent was obtained by modification of chitosan with3-benzylsulfanyl thiocarbonylsulfanyl propionic acid (BPATT). The graft copolymer was generated successfully suggesting the chain transfer agent was stable in the process of polymerization, and that the graft polymerizations of AA and NIPAAm were a first-order reaction with respect to monomer concentrations and reation time. The graft copolymer assembled to micelles in aqueous solution with narrow distribution in dependence of the formation of branch chains, temperature and pH. The micelle response behavior to temperature and pH was confirmed by DLS and UV-visible spectrophotometer. The LCST values of micelle could be modulated by controlling the formation of branch chains, pH, and concentration.