Studies On Preparation Of Polysaccharide-based Graft Copolymers And Their Self-assembly In Water

Water-soluble polymeric nanoparticles hold great potential applications in the field of biomedicine due to their low critical micelle concentration (cmc) and high stability. Self-assembly of amphiphilic copolymers has been widely used to prepare the nano-sized micelles in water where the hydrophobic block forms the core and the hydrophilic one forms the shell. However, it is inevitably to use an organic solvent as the common solvent at the initial stage of the preparation. Both the organic solvent and the hydrophobic blocks usually do not meet the requirement of complete biocompatibility which is often necessary in biomedicine applications. With the development of biomedicine and nano-engineering technology, there are several new concepts which show progressively increasing importance in the studies of polymeric micelles: (1) Double-hydrophilic: a double-hydrophilic block (graft) copolymer consists of two blocks (water-soluble main and graft chains) with hydrophilicity or environment-responsive hydrophilicity. At certain conditions, one kind of the block promotes dissolution, whereas the other associates to form micellar core. In addition, a change in temperature or pH, as well as complexation with appropriate molecules, can induce micelle formation as well. (2) stimuli-responsibility: polymeric nanoparticles can response to external stimuli, such as pH, temperature, ionic strength, electricity and light, etc., to change their morphology or shift the equilibrium between the single molecules and micelles, etc. (3) bio-compatibility: it is the necessary requirement of the materials used in the area of biomedicine. (4) hollow sphere: the polymeric nanoparticles with a central cavity have a great potential for encapsulation of large quantities of guest molecules or large-size gust molecules. (5) high concentration: In the conventional self-assembly approach to polymeric micelles, normally the solution concentration has to be very low (<5mg/ml), which means a poor efficiency of production. Obviously, new approaches which can be performed at higher concentration favors the mass-production of the micelles.In this thesis, we designed our work on self-assembly of copolymers by taking these new concepts account as much as possible. We have prepared a series of graft copolymers having selected polysaccharides as the main chain, which is water-soluble and biodegradable. Somehydrophilic synthetic polymers served as grafts. Depending on the nature of the grafts, composition, temperature, pH value, the degree of crosslinking, etc. we are able to fabricate a variety of micelles and hollow spheres in water. In some cases, the preparation can be performed at high concentration. In addition, a reversible pH-dependent transition between micelles and hollow spheres was observed.(1) water-soluble copolymers with cellulose ether-hydroxyethyl cellulose (HEC) as main chain and polyacrylic acid (PAA) as graft were prepared by free-radical polymerization. The products were characterized: after degradation of cellulose, pure PAA grafts were recovered and then their molecular weight was determined by viscosity measurement. Graft density was also calculated. DLS and SLS were used to get the Mw, ?Rh>of the copolymers.(2) The pH-induced micellization of HEC-g-PAA was found. Depending on pH values, the HEC-g-PAA solution shows different behavior which can be divided into three regions, i.e., stable micelle regime (Regimeâ…¢), unstable micelle regime (Regimeâ…¡) and soluble regime (Regimeâ… ). The graft copolymer forms micelles when pH decreases to about 3, the micellization is caused by hydrogen-bonding complexation between the proton-acceptors in HEC and the proton-donors in PAA. The micelles show distinct core-shell structure as observed by TEM and SEM. Besides, temperature has obvious influence on the micellization in regime â…¢, as the diameter of micelles increases with rising temperature.(3) Core-crosslinking of the PAA chains in the HEC-g-PAA micelles in acidic medium resulted in stable nanoparticles. The crosslinked micelles...