Preparation And Properties Study Of Nanocomposite Hydrogels With Integrated Structure/Function And Novel Hydrophilic Thermo-Responsive Block Copolymer Micelles

Due to their unique structure and physical and chemical properties, polymer hydrogel attracts interests in many fields, especially in biomedical application. In order to improve the poor mechanical behavior and shortage of functions presented in conventional polymer hydrogels, different network structures were designed to decrease or disperse stress concentration caused by external forces. Meanwhile, methods like redesigning the molecular or network structures, introducing functional inorganic nanoparticles were also used to introduce new performances into hydrogels or increasing their stimuli-responsive rate. However, researches on possessing good biomedical properties without compromising mechanical performances in the same hydrogel system still need to be further explored.Organism internal changes in the microenvironment (e.g. temperature, pH, ionic strength) can trigger the hydrophilic-hydrophobic conformational transition of hydrophilic block copolymers. On the basis of this theory, hydrophilic block copolymer micelles are able to be design as an ideal drug delivery and controllable release system. So far, poly(N-isopropyl acrylamide)(PNIPAAm), which display a LCST in water around32℃, has been the most studied thermo-sensitive polymer in applied block copolymer micelles. However, in addition to the toxin of NIPAAm monomer, slight variations of environment are generally affecting the LCST of PNIPAAm by a few degrees only. Moreover, although covalently connect polymer chains together (cross-linking) is an effective way to overcome such a shift in the equilibrium between polymeric micelles and non-associated single polymer chains, but the performance of non-cross-linked micelles and cross-linked micelles in practical applications remain further compare and analyses.Facing the problems above, this thesis was designed and carried out with two parts. The first part was to study on the integration of anti-bacterial function and service performance in a PAAm-based hydrogel. In this part, surface modification of commercial ZnO nanoparticles (ZnO NPs,300nm in diameter) were carried out by using polymethylacrylic acid (PMAA) chains. And by using the modifed-ZnO NPs (mZnO NPs) and N,JV’-methylene-bis-propanamide (BIS) as physical and chemical cross-linker, respectively, novel antibacterial mZnO/PAAm nanocomposite hydrogels with double physical/chemical cross-linked structure were prepared via redox initiated polymerization. FTIR, TGA and SEM were used to study the surface modification of ZnO NPs and the prepared mZnO/PAAm nanocomposite hydrogels. Mechanical properties, swelling behavior and antibacterial effect of the hydrogels were also investigated. Results showed that mZnO NPs dispersed uniformly in both aqueous solution and hydrogels’ network due to hydrogen bond interactions between-OH groups on the surface of mZnO NPs and-COOH groups on covered PMAA chains (the cover ratio was3.44wt%) and served as a physical cross-linker. It was also revealed that in correspond to the content of physical and/or chemical cross-linkers, the mechanical properties and swelling behavior (swelling ratio) of those hydrogels could be controlled within140-800kPa and55-170%, respectively. Further antibacterial test illustrated that such ZnO NPs implanted hydrogels inhibited the growth of several kinds of oral anaerobes. These hydrogels may provide a simple approach to achieve the integration of structure and function.In the second part, in order to prepare hydrophilic block polymers with biocompatibility and controllable LCST, macroinitiator MPEG2000-Br and monomer N-methacryloyloxysuccinimide (NAS) were synthesized. Then, by using thermo-sensitive PEG analogues2-(2-methoxyethoxy)ethylmethacrylate (MEO2MA), oligo(ethylene glycol) methacrylate (OEGMA, Mn-475g/mol) and NAS as cross-linking appendents, MPEG2000-Br as macroinitiatior, a series of hydrophilic thermo-responsive PEG45-b-P[(MEO2MAx-co-OEGMA1-x)5o-co-NASy] block copolymers were prepared via ATRP polymerization.’H NMR and GPC were used to confirm the structure, molecular weight and distribution of the synthesized macroinitiatior, monomer and copolymers; UV-vis were used to study the thermo-responsive behavior of the copolymer in aqueous and salt electrolyte solution; DLLS, fluorescence spectroscopy and TEM were used to analyze the self-assembly behavior of the synthesized copolymer. Release kinetics against aqueous and phosphate buffer solution (PBS, pH=7.4) of non-cross-linked (NCL) and core-cross-linked (CCL) copolymer micelles were also carried out. Results show that macroinitiatior, monomer and copolymers were successfully synthesized and had uniform distribution. By altering the concentration of OEGMA in a unimer, the LCST of PEG45-b-P(MEO2MAx-co-OEGMA1-x)50raised from36.9℃to87.5℃, which suggested that polymers reached biological temperature closely when only composed by MEO2MA. And it was additionally observed that LCST values decreased as the salt concentration and anion valence increased. The critical micelle temperature (CMT) of copolymers observed from DLLS matched that from UV-Vis and critical micelle concentration (CMC) of PEG45-b-PMEO2MA50copolymer was0.045mg/mL, which was much lower than any polymer concentration chosen in experiments. Release kinetics experiments in both aqueous and PBS showed that varying degrees of rapid release of Nile Red were observed in the first8hours under both25℃and37℃despite from NCL micelles or CCL micelles. And CCL micelles released Nile Red slowly in the next42hours. When reaching the balance of release, the cumulative release rate of Nile Red from CCL micelles was obviously lower than that from NCL micelles, which proved that CCL micelles had more stable structure and provided better protection to loaded drugs models.