| Amphiphilic polymers are composed of hydrophilic and hydrophobic segments.Amphiphilic polymers with versatility are synthesized by means of selection of structure or polymerization unit,regulation of degree of polymerization,proportion of different structural units,and modification of functional groups at the ends of the polymer chain,and they can be formed with"Core-shell"structure,vesicles,hydrogels,and nanoparticles in aqueous solutions.The"Core-shell"structure nanomicelles can encapsulate lipophilic drugs by non-bonding or chemical bonding during micelle formation.Compared with small molecular surfactants,this kind of micelle,vesicle,hydrogel nanoparticles has a lower critical micelle concentration and slower micelle-single molecule exchange rate,which are more suitable for carrying fat soluble drugs and nutrients.However,most of the amphiphilic polymers have the disadvantages of low release rate and poor acid-sensitivity.For that reason,This paper has been designed,synthesized and functionalized for biocompatible amphiphilic polymers.We used these polymeric micelles to deliver hydrophobic drug?VE?and study the vitro release effect.The main contents and conclusions of this dissertation are summarized in the following aspects:1?The amphiphilic block copolymers MA-PEO-SS-PCL was synthesized via the organic catalysis ring-opening polymerization,using nuclear magnetic?HNMR?,infrared spectra?FTIR?and gel permeation chromatography?GPC?analysis method to analyze the characterization.The critical micelle concentration?CMC?of the polymer was determined by pyrene-fluorescence spectroscopy.DLS and TEM were used to measure the blank and drug-loaded micelle.Results show that the preparation of the amphiphilic polymer molecular structure consistent with design structure,critical micelle concentration of 2.10×10-3 g/L,in aqueous solution can self-assemble into regular spherical nanometer micelle,before and after drug micelle size respectively in 30 nm and 60 nm,PDI was 0.27 and 0.16,respectively.Methylene blue test method,conductivity method and zeta potential determination results show that the preparation of the amphiphilic polymer has good responsiveness to weak acid.Under the condition of pH<7,Polymer micelles can be protons and take a positive charge,electric conductivity of 1.3×10-2 g/L,zeta potential>0 mV,vitamin E of model drug envelopment rate of 80%,delivery rate of 15.6%.When pH=7.4,it can release about 15%of the Drug loading efficiency in 50h;When pH=7.4 and GSH?10uM?,about 20%of the drug can be released in 50h;When pH=7.4 and GSH?10mM?,it can release about 28%of the drug load in 50h.When pH=5.0,it can release about 19%of the load in 50h;When pH=5.0 and GSH?10 uM?,it can release about 30%of the dosage in 50h;When pH=5.0 and GSH?10mM?,it can release about 60%of the dosage in 50h.The TEM results showed that when the micelle was stimulated with GSH for 24h,the particle size was larger and the micelle was destroyed,indicating that the carrier micelle had a good responsiveness to GSH.In addition,the results of MCF-7 cytotoxicity test showed that the survival rate of the cells was still up to 90%when the micelle concentration was 250?g/mL,and that the micelles formed by the MA-PEO-SS-PCL material had very low toxicity to MCF-7 cells.2?The morpholine acetate polyethylene glycol-polylactide copolymer?MA-PEO-PLA?was prepared by esterification reaction and ring-opening polymerization.The yield of the reaction was about 56.7%.By clicking reaction,the weak acid responsiveness of 1-?2-Dimethylaminoethyl?-5-Mercapto-1,2,3,4-Tetrazole?DMMT?with ally-PEO-PLA covalent bonds in preparation for DMMT hydrophilic chain end group of amphiphilic copolymer DMMT-PEO-PLA,The reaction yield was?92%.The reactivity of the click reaction is significantly higher than that of the esterification reaction,and the synthesis conditions are mild,and the reaction is carried out at room temperature at atmospheric pressure,which has good applicability.The above products were characterized by HNMR and GPC.the self-assembly behavior of in aqueous solution was studied by pyrene-fluorescence probe method,dynamic light scattering?DLS?and transmission electron microscopy?TEM?method,results show that:?1?low critical micelle concentration(1.45×10-3g/L);DMMTt-PEO-PLA can be self-assembled into spherical nano micellar in aqueous solution,and the encapsulation rate of vitamin E is 85%.Before and after loading,the nano-micelle was increased from 45nm to 60nm.In the case of pH=5.0,the cumulative release efficiency of DMMT-PEO-PLA micellar with VE was35%.The results of MCF-7 cytotoxicity test showed that the survival rate of the cells was more than 90%when the micellar concentration was lower than 250?g/mL,and the two pro-ionic polymer DMMT-PEO-PLA have good biocompatibility.In addition,the dynamic light scattering?DLS?monitoring results show that the DMMT-PEO-PLA micelle with VE has a good storage stability performance,and there is no significant change in particle size and PDI of the micelles in 35 days. |
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