Synthesis And Characterization Of Several Amphiphilic Polymer Compounds And Their Micellar Research

Poly(butylene succinate)(PBS),is a kind of commoditized polymer materials with good stability,low glass transition temperature,a complete biodegradability and bioabsorbability.Due to these advantages,PBS has a broad application prospect as drug control-released carriers.However,most of the studies on PBS polymers focuse on the thermal and crystal properties of PBS copolymers and,blends,there is little research on their biomedical application as drug control-released carrier.The main obstacles of PBS polymers using as excellent drug control-released carrier are their strong hydrophobicity and poor biocompatibility which made them cannot keep stabilization in vivo for a long time.So,to improve the biocompatibility of PBS polymers,the modification of PBS is necessary.How to select suitable monomers or methods to modify PBS is a key problem to broad its application scope.Phosphorylcholine,referred to as the PC group,is composed of cell's outer membrane hydrophilic end group with excellent hydrophilic properties.Numerous studies showed that the introduction of PC group or monomer with PC into the polymer structure can largely increase the hydrophilicity of material,and enhance the biocompatibility of materials.Based on bionics,combined the classical condensation polymerization and atom transfer radical polymerization(ATRP),a series copolymers of PBS modified with PMPC,PMPC-PBS-PMPC were synthesized.The PC group gives these copolymers excellent biocompatibility,copolymers of PMPC-PBS-PMPC can self-assemble into nanomicelles with the structure of mimicking cell outer membrane,which greatly prolong the circulation time in vivo and can be concentrated upon tumour cell through the EPR effect.The main work of this thesis is as follows:(1)Hydroxyl terminated poly(butylene succinate)was synthesized through the classical condensation polymerization,and then by the reaction of PBS and 2-bromoisobutyryl bromide,the macroinitiator PBS-Br was synthesized.Finally,the ATRP was being carried out between PBS-Br and MPC,using chloroform and methyl alcohol as a mixed solvent to synthesize copolymer PMPC-PBS-PMPC.In order to study the relationship between the structure and performance,three different copolymers were synthesized in this study.The results of hydrogen nuclear magnetic resonance spectrum(1H NMR),carbon nuclear magnetic resonance spectrum(13C NMR),infrared spectroscopy(FT-IR)and x-ray photoelectron spectroscopy(XPS)confirmed the successful synthesis of the copolymer.(2)Copolymers of PMPC-PBS-PMPC can self-assemble to nanomicelles in water by the solvent evaporation method.Furthermore,the impacts of the concentration and MPC content of copolymers on micelle size and distribution were discussed by dynamic light scattering(DLS).Transmission electron microscope(TEM)and 1H NMR were both used to illustrate the core-shell structure of nano-micelles.Cytophagy experiment proved that PMPC-PBS-PMPC polymeric micelle has a good invisibility effect,cytotoxicity experiment demonstrated low toxicity of micelle.(3)Using doxorubicin as a model drug,drug loading and releasing of PMPC-PBS-PMPC polymeric nano-micelles were studied.Furthermore,the effect of the amount of initial drug and the proportion of PC in the copolymer on micelle size,distribution,loading efficiency and encapsulation efficiency was discussed.Then the drug release kinetics were studied through model-fitting method.