Preparation And Self-assembly Behavior In Aqueous Solution Of Thermosensitive Polymer Based On Hydroxyethyl Cellulose

Polymer micelles have been intensively investigated in every fields of biomedicine. They enjoy several advantages over other particulate configurations, which include low critical micelle concentration(cmc) that render the drug-loaded micelles stable in the blood stream to achieve long-circulating time, bio-compatibility, etc. 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, both the organic solvent which is the common solvent at the initial stage of the preparation 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 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 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 micelles 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.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 temperature-sensitive block/graft copolymers having selected cellulose ether-hydroxyethyl cellulose (HEC) as the main chain, which is water-soluble and biodegradable, and N-isopropylacrylamide (NIPAAm) as monomer. Depending on changing temperature, we are able to fabricate a variety of micelles in water.(1) The double-hydrophilic HEC-b-PNIPAAm copolymer was creatively synthesized by a block polymerization of HEC from amino-terminated poly(N-isopropylacrylamide) (PNIPAAm-NH2). Successful preparation of copolymer was verified by FTIR and NMR spectra. The molecular weight of HEC and copolymer were measured by GPC and SLS.(2) The thermally induced micellization of HEC-b-PNIPAAm in water has been found. Large particle having hydrodynamic radii() between 400 and 600 nm were formed above LCST. The test showed that the LCST of copolymer was around 32℃by UV and DSC. The critical micelle concentration (CMC) was measured by fluorescence and surface tention measurements. DLS and SLS were used to investigate the formation of micelle structures, exhibiting the tendency to larger polymolecular micelle when the temperature exceeded the LCST with increasing final copolymer concentration and time at constant temperature. TEM study showed that the morphology of the...