| Breast cancer is a high incidence of cancer,a serious threat to human health.Since its discovery,paclitaxel(PTX)has been widely used because of its excellent therapeutic effect on breast cancer.However,in clinical application,paclitaxel has some problems,such as poor water-solubility,high blood clearance rate,and high toxic and side effects,which seriously affect its therapeutic effect.In order to solve the above problems,this study used the early discovery with characteristics of supramolecular self-assembly of betulonic acid(BTA),through the emulsification-solvent evaporation method,constructed a birch keto acid-composite nano drug taxol system(BTA-PTX NPs),using betulonic acid self-assembly properties of nano drug system not only implements for targeted delivery of taxol and slow release,also has good biocompatibility and safety.The main contents and results of this study are as follows:Using solvent method right through to the target component is extracted,using column chromatography for separation and purification,identified target component spectrum and spectrum analysis for betulonic acid,through the emulsification-solvent evaporation method to construct betulonic acid self-assembled nanoparticles drug system,and the three main factors affecting the formation of the nanostructures,emulsifier type,variety of organic solvents,and oil/water ratio is optimized,determine the best process parameters: emulsifier for polyvinyl alcohol(PVA),organic solvents for methylene chloride,oil-water ratio is 1:3.On this basis,the optimum ratio of BTA-PTX NPs is 20:7,which can form regular spherical nanostructures.The morphology and structure of BTA-PTX NPs were characterized by SEM,TEM and DLS.The particle size of BTA-PTX NPs was 257.4± 2.4nm and PDI was 0.07±0.01,showing regular spherical nanostructure.Through in vitro BTA loading and PTX release experiments,the optimal loading amount and the encapsulation rate were 33.12% and 87.8% respectively.According to the results of UV,IR and contact Angle experiments,non-covalent bond interaction between betulonic acid and paclitaxel was found,which was the reason for the formation of BTA-PTX NPs nanocomposite.In vitro and in vivo studies on the treatment of breast cancer were carried out by constructing betulonic acid-paclitaxel nanodrug system.The results showed that BTAPTX NPs had higher cytotoxicity on 4T1 and MCF-7 breast cancer cells.The IC50 value of BTA-PTX NPs on 4T1 cells was 2.13 g/m L,significantly lower than that of PTX(5.72 g/m L).The IC50 value of BTA-PTX NPs on MCF-7 cells was 2.28 g/m L,which was significantly lower than that of PTX on 4T1 cells(6.53 g/m L),and was obtained by endocytosis in both cancer cells.The results of animal experiments in vivo showed that BTA-PTX NPs could rapidly reach tumor tissue sites through passive targeting(EPR effect),and the tumor growth inhibition rate was 70.4±7.5%,significantly higher than that of paclitaxel(48.5±7.3%).The safety of betulonic acid-Paclitaxel nanodrug system was evaluated in vitro and in vivo.In vitro cell test results showed that BTA-PTX NPs showed no toxicity to normal LO2 cells.In vivo experiments showed that BTA-PTX NPs did not cause abnormal blood biochemical indexes,nor did it cause weight loss or damage to the main organs of the animals.These results show that BTA-PTX NPs not only has good anti-tumor activity,but also has good safety and low toxicity.Therefore,this study constructed a betulonic acid-paclitaxel nano-drug system,which has good anti-tumor effect and low toxic and side effects,and shows good application potential in the treatment of breast cancer.Therefore,this study constructed a betulinic acid-paclitaxel nano-drug system,which has good anti-tumor effect and low toxic and side effects,and shows good application potential in the treatment of breast cancer. |
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