Preparation And Propert Ies Of Thermo-Sensitive Copolymer Composite Micelles

The copolymer single micelles as the drug carrier have much instability.Composite micelles composed of two block copolymers can improve the stability of the micelle structure and the encapsulation efficiency of the drug.Based on the above reasons,two kinds of block polymers were synthesized and prepared as the building units of the novel copolymer composite micelles.The research contents are as follows:?1?Polyethylene glycol monomethyl ether?MPEG?and N-vinylcaprolactam?NVCL?were used as the raw materials,terminal amino polyethylene glycol monomethyl ether?MPEG-NH₂?and terminal amino poly-N-Vinyl caprolactam?PNVCL-NH₂?were prepared respectively.They were used as a macroinitiator to initiate ring-opening polymerization of L-aspartic acid-N-ring anhydride?BLA-NCA?to prepare polyethylene glycol monomethyl ether-b-poly-L-aspartic acid benzyl ester?MPEG-b-PBLA?and poly-N-vinylcaprolactam-b-polyaspartic acid benzyl ester?PNVCL-b-PBLA?block copolymer.IR,¹H NMR and GPC were used to characterize the structure of the copolymer.The absorbance of PNVCL-b-PBLA at different temperatures was tested by UV-Vis spectrophotometer,and the LCST temperature of it was 35°C.?2?MPEG-b-PBLA were used to prepare the copolymer single micelles?SM?which has MPEG as its shell and PBLA as its core.MPEG-b-PBLA and PNVCL-b-PBLA were used to prepare copolymer composite micelle?CM?which has PBLA as its core,PNVCL and MPEG as as its mixed shell.The particle size distribution and morphology of the micelles were investigated by transmission electron microscopy?TEM?and dynamic light scattering?DLS?.The entrapment,release properties and cytotoxicity of two micelles on doxorubicin?DOX?were studied.The results showed that the particle size of SM and CM was uniform and the size was at 70-170 nm.The drug loading rate and drug loading of CM are superior to those of the SM which have core-shell structure.In vitro release experiments showed that the release rate of composite micelles at 37°C was less than that at 25°C,the release rate of micelles at pH 5.0 was greater than that at pH 7.4,and the release rate of the composite micelles with the polymer molar ratio of 3:2 were greater than that of 1:1 and greater than 2:3.MTT experiments of blank micelles showed that both micelles showed lower toxicity to A549 cells.MTT experiments of drug-loaded micelles showed that the composite micelles had a better encapsulation effect.Endocytosis experiments showed that the composite micelles could be endocytosed into the cytoplasm by A549 cells and release the encapsulated drugs therein.