Synthesis Of Amphiphilic Polymer Materials And Its Application In Drug Carrier

Recently, with the development of biomedical materials, there have been various types of polymers in the scientific community, polymers with special chemical structure and molecular configuration attracted wide attention for their smart and environment response. Stimuli-sensitive materials usually have special chemical structure and chemical constitution, which can be used to prepare drug delivery carrier with specific function, for example, the temperature-sensitive hydrogels, pH-responsive micelles and so on.Poly (s-caprolactone) (PCL), poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) which were approved by the US Food and Drug Administration(FDA), were employed as the matrices. In the first part, hydrogen peroxide (H2O2)-responsive polymers PEG-PO-PCL-PO-PEG were synthesized with peroxyoxalate (PO) as the linker. In the second and third part, multi-arm shaped copolymers PLGA-PEG and different molecular weight six arm shaped copolymers PCL-PEG were synthesized by esterification with oxalyl chloride. Micelles prepared by these polymers were evaluated and selected for the optimal drug delivery carriers.The first part:Liner PCL was synthesized by ring-open polymerization and PCL with terminal phenolic group was obtained by esterification with 4-hydroxybenzoyl chloride, then H202-responsive PEG-PO-PCL-PO-PEG was synthesized by esterification with oxalyl chloride. Fourier-transform infrared (FTIR), gel permeation chromatography (GPC), hydrogen nuclear magnetic resonance spectrum (’H NMR) and differential scanning calorimetry (DSC) were employed to identify the structure and properties of polymers. Micelles were prepared by solvent evaporation method. Pyrene was used as the fluorescence probe to detect the critical micelle concentration (CMC) of copolymers. The H2O2 responsive property of these polymers was proved by analysis the change of particle size, the difference of release behavior in H2O2 solution and PBS buffer. Results showed that H2O2-responsive PEG-PO-PCL-PO-PEG was suitably used as drug release carrier and had promising application in H2O2 overproduction diseases.The second part:Liner, three and six arm-typed polymers PLGA with terminal phenolic group were synthesized by ring-open polymerization, then multi-arm typed polymers PLGA-PEG were obtained by esterification with oxalyl chloride. FTIR, GPC, 1H NMR and DSC were employed to identify the structure and properties of polymers. Micelles were prepared by solvent evaporation method. Pyrene was used as the fluorescence probe to detect the critical micelle concentration (CMC) of copolymers. The size of multi-arm polymeric micelles were characterized by DLS, the sizes of 3S-PLGA-PEG and 6S-PLGA-PEG micelles were smaller and L-PLGA-PEG micelles was the largest, which provided the reference for next drug-loading, drug release and cell proliferation experiment.The third part:Six arm star-shaped polymers PCL with different molecular weight were synthesized by ring-open polymerization then PCL-PEG copolymers were obtained by esterification with oxalyl chloride. In this experiment, the effect of molecular weight on the polymers as drug carrier was studied. FTIR, GPC,1H NMR and DSC were employed to identify the structure and properties of polymers and micelles were prepared by solvent evaporation method. Pyrene was used as the fluorescence probe to detect the critical micelle concentration (CMC) of copolymers. By characterization of polymers and micelles,6S-PCL200-PEG micelles had uniform particle size which was suitable as drug delivery carriers. However,6S-PCL100-PEG micelles had broad particle size and 6S-PCL300-PEG micelles appeared much precipitation which indicated that these polymers were difficult to form stable micelle solutions.