Preparation And Properties Of Sulfobetaine Polymer Micelles With PH Responsiveness

Most anti-tumor drugs have shortcomings with poor water solubility,short half-life,large side effects,and low therapeutic efficiency.In order to solve this problem,polymer micellar carriers appeared.Micellar carriers can increase the solubility of tumor drugs,reduce their side effects,and improve the efficiency of treatment.However,such nanocarriers often have disadvantages such as poor stability,short half-life of blood circulation,and slow release efficiency.In this paper,we designed and synthesized an amphiphilic polymer to improve the micelle circulation time and increase the drug release efficiency.Through simple free radical polymerization,ring-opening polymerization and other reactions,we have synthesized a copolymer PCDS containing hydrophobicity PCL group,hydrophilic sulfobetaine zwitterion and acid sensitive group.And then we study the thermal properties of the polymer,the hydrophilic and hydrophobic properties of the coating,and its self-assembly to form micelles.The main contents of this thesis are as follows.1 Synthesis and characterization of sulfobetaine zwitterionic copolymer.First,PDMAEMA is prepared by mercaptoethanol initiating DMAEMA,Then the reaction activity of the terminal hydroxyl of PDMAEMA-OH is used to initiate ring-opening polymerization ofε-caprolactone to obtain the block copolymerization PCL-b-PDMAEMA,this is PCD;Finally,the target polymer PCDS is obtained by controlling the feed ratio of 1,3-propane sultone and PCD.In order to study the influence of polymer composition on its own properties and the properties of self-assembled micelles,we synthesized 25%PCDS and 50%PCDS.and 75%PCDS.The structure and composition of the polymer were determined by ~1H-NMR,IR and GPC.2 Study on the performance of sulfobetaine polymer and its coating.The thermal performance of the polymer was characterized by TG.The results showed that the thermal decomposition of the copolymer was carried out in stages,and the introduction of PDMAEMA or SB groups did not reduce the thermal decomposition temperature of the polymer.;The crystallization performance of the polymer was characterized by DSC and XRD.The results showed that with the introduction of PDMAEMA or SB groups and the increase in the content of SB groups,the crystallinity of the polymer was reduced to a certain extent.The method of physical coating is used to construct a polymer coating.Through X-ray photoelectron spectroscopy(XPS),the element composition and content of the coating were studied.XPS showed that the coating was successfully prepared,and the element content on the surface of the coating was quantitatively analyzed.The hydrolytic tentacles(WCA)were used to characterize the hydrophilic and hydrophobic properties of the coating.The results showed that the PCDS polymer coating has good hydrophilic properties and has dual response characteristics of pH and salt concentration.3 Study on the self-assembly of sulfobetaine zwitterionic copolymer.The blank polymer micelles and drug-loaded micelles of PCD,25%PCDS,50%PCDS and 75%PCDS were prepared by solvent evaporation method.Dynamic light scattering(DLS)showed that the particle size of the micelles were all in below 200 nm.And it was proved by XRD that DOX was encapsulated into the micellar core.Then the critical micelle concentration of micelles was measured by pyrene fluorescence method,and the results showed that it has good anti-dilution ability.Using DLS,it was confirmed that micelles have salt and pH responsiveness.And then we evaluated its drug release capacity in vitro The results showed that the drug release of PCD,25%PCDS,and 50%PCDS in PBS buffer medium at pH 7.4 was slower than that in PBS buffer medium at pH 5.0,while the drug release experiment of 75%PCDS micelles did not obvious pH responsiveness In cell experiments,the toxicity of blank PCD micelle to L929,He La and MCF-7 was significantly higher than that of the other three blank micelles.The toxicity of drug-loaded micelles to normal cells L929 is lower than the same amount of free adriamycin,while PCD,25%PCDS,and 50%PCDS micelles are more toxic to He La and MCF-7 cells.The lower 75%of PCDS is less toxic.In the laser confocal experiment,it was found that the drug-loaded micelles were all endocytosed into the cell,and comparing the fluorescence intensity of the four micelles after endocytosis,50%PCDS micelles had the highest endocytosis efficiency.