| This experiment synthesized six groups of amphipathy polyphosphazenes with different physical and chemical properties.polyphosphazenes as skeleton by choosing aluminium chloride as catalyst,six chlorine ring there thermal polymerization synthesis,pentapeptide(Z-GFLGK)and heptapeptides(Z-GFLGK)as the hydrophobic chain segments which are sensitive to enzyme,MPEG as the hydrophilic chain segments.By changing the MPEG and polypeptide malor ratio,the six groups amphipathy polymer have different affinity-disaffinity water ratio and the types of peptides.This series of polymer are easy to form micelle particles by self-assembly behavior in aqueous solution,they have unique shell-nuclear structure,and can be stable in the water.The structural characterization of six groups enzyme response polyphosphazenes through nuclear magnetic resonance hydrogen spectroscopy(1H-NMR),ultraviolet visible spectrum(UV)and infrared spectroscopy(FT-IR).Pyrene fluorescence probe method was used to study the self-assembly behavior of this series of polymer in aqueous solution.According to the fluorescence intensity and the logarithm of the corresponding polymer concentration we have drawn curve,and measured six groups of copolymer minimum critical micelle concentration(CMC).The results revealed that the CMC decreases gradually with the increase of the proportion of hydrophobic chain in polymer.Using dynamic light scattering(DLS)and atomic force microscope(AFM)to study the series of polymer micelle size,particle size distribution and existing morphology in aqueous solution.The measurement results of DLS show that mean particle size of micelle in 20 to 50nm range and distribution is single status;AFM observed micelle particles exist in spherical form and in conformity with the results determined by DLS.The synthesis of six groups of enzyme response type polymer as carrier material,preparation of twelve groups of polymer carrying drugs,though covalenting bond small drugs molecule adriamycin-cis aconitum anhydride(CAD)sensitive to acid and adriamycin-succinic anhydride(SAD)insensitive to acid on its side chain.By ultraviolet spectrometry measured drug loading capacity of copolymer.The results showed that the more greater of the proportion of peptides in polymer the more drug loading,and two groups polymer with different polypeptide chain segment showed similar trend and the drug loading were above 10%.Using DLS and AFM to study drug-loading micelles.The results of DLS show that micelle particles are still single distribution condition,but particle size became significantly bigger with increase of drug-loading and the mean particles size seem 100nm or so;AFM observed micelle particles exist spherical with the results of DLS.We also studied the properties of drug-loading polymer micelle in vitro release.Choosing different pH(5.0,6.8,7.4)of phosphate buffer medium as dissolution medium to study the drug release performance of micelle in different pH environment within 72h.Experimental results show that the pH of the environment has a great influence on the release of micelle drug-carrying bonding acid sensitive CAD molecular polymer,and the release rate of adriamycin in the core of micellar is slower under higher pH,and cumulative release percentage is low within 72 h;while,the cumulative release percentage rise sharply with the reduction of pH,and release rate as high as 80%.Because the dissociation of acid sensitive CAD in drug micelle kernel under low pH,increased the solubility and the accelerate release of adriacin doxorubicin.However,the pH of release environment has little impact on the release rate of bonding SAD molecular polymer,and the cumulative release percentage all below 20%. |
