肿瘤靶向oHA-VES纳米聚合物胶束载体的构建与评价
发布时间：2018-09-08 19:10
【摘要】：目的合成并表征两亲性嵌段聚合物寡聚透明质酸-维生素E琥珀酸酯(oHAVES),制备载多西他赛oHA-VES/F68混合聚合物胶束并考察其理化性质,并对HAVES/F68-DTX进行体外和体内的评价。方法将透明质酸(oHA)与维生素E琥珀酸酯(VES)通过酰胺反应合成两亲性嵌段聚合物载体材料。超声法制备oHA-VES/F68混合聚合物胶束,对oHA-VES/F68的形态、粒径、Zeta电位、包封率、载药量和体外释放进行考察,通过芘荧光探针法考察聚合物的临界胶束浓度值(CMC)。采用透射电镜(TEM)、马尔文动态光散射粒径仪对聚合物胶束的形态、粒径大小及Zeta电位进行表征;采用透析法考察体外释放。红外法(FTIR)和核磁共振氢谱(1H NMR)鉴定oHA-VES的合成。采用MTT法考察MCF-7细胞的细胞毒性。以DiR染料作为荧光探针用荷瘤小鼠体内活体成像技术测定聚合物胶束在24h后小鼠体内的荧光强度。结果通过酰胺化反应合成oHA-VES聚合物载体材料,采用超声法制备oHAVES/F68混合聚合物合物胶束。所制得的oHA-VES/F68-DTX的粒径、Zeta电位、包封率、载药量分别为(91.2±7.51)nm,(-10.4±0.47)mV,(80.36±1.54)%,(2.69±0.26)%。透射电镜下观察oHA-VES/F68-DTX的粒子呈球形,形态圆整,分散均匀。72 h累积释放率为80.74%。CCK-8法测定DTX对MCF-7细胞的IC50值为9.7μg·mL-1,oHA-VES/F68-DTX有较大的细胞毒性,oHA-VES空白载体基本无细胞毒性。活体成像表明,oHA-VES/F68聚合物胶束在体内能够显著提高聚合物胶束的靶向性。结论通过超声法成功制备了oHA-VES/F68-DTX聚合物胶束,所采用的制备方法简便可行。具有一定缓释性能的oHA-VES/F68-DTX的粒径、包封率较好。体外细胞实验表明,oHA-VES/F68-DTX对细胞有明显的毒性作用。体内试验表明,oHA-VES/F68-DTX聚合物胶束具有显著的靶向性。oHA-VES是一种可将DTX递送到肿瘤细胞的有效的载体。
[Abstract]:Aim to synthesize and characterize amphiphilic block polymer oligomeric polyhyaluronic acid-vitamin E succinate (oHAVES),) to prepare mixed polymer micelles containing docetaxel (oHA-VES/F68) and investigate their physicochemical properties and evaluate HAVES/F68-DTX in vitro and in vivo. Methods Amphiphilic block polymer carrier material was synthesized by the reaction of hyaluronic acid (oHA) with vitamin E succinate (VES). OHA-VES/F68 mixed polymer micelles were prepared by ultrasonic method. The morphology, particle size and Zeta potential, entrapment efficiency, drug loading and in vitro release of oHA-VES/F68 were investigated. The critical micelle concentration (CMC).) of the polymer was investigated by pyrene fluorescence probe method. The morphology, particle size and Zeta potential of polymer micelles were characterized by transmission electron microscope (TEM),) Ma Erwen dynamic light scattering particle size analyzer and dialyzed method. The synthesis of oHA-VES was identified by IR (FTIR) and 1H NMR. The cytotoxicity of MCF-7 cells was investigated by MTT assay. The fluorescence intensity of polymer micelles in mice after 24 hours was measured by in vivo imaging technique using DiR dye as fluorescence probe. Results oHA-VES polymer carrier materials were synthesized by amidation reaction, and oHAVES/F68 mixed polymer micelles were prepared by ultrasonic method. The particle size potential, encapsulation efficiency and drug loading of oHA-VES/F68-DTX were (91.2 卤7.51) nm, (-10.4 卤0.47) mV, (80.36 卤1.54) and (2.69 卤0.26), respectively. Under transmission electron microscope, the particles of oHA-VES/F68-DTX were spherical and round in shape. The cumulative release rate of DTX for 72 h was determined by 80.74%.CCK-8 method. The IC50 value of DTX to MCF-7 cells was 9.7 渭 g mL-1,oHA-VES/F68-DTX. There was no cytotoxicity in the blank carrier of DTX HA-VES. In vivo imaging showed that the polymer micelles of OHA-VES / F68 could significantly improve the targeting of polymer micelles in vivo. Conclusion the oHA-VES/F68-DTX polymer micelles were successfully prepared by ultrasonic method, and the preparation method is simple and feasible. The particle size and encapsulation efficiency of oHA-VES/F68-DTX with certain slow release properties were better. In vitro cell experiments showed that OHA-VES / F68-DTX had obvious cytotoxicity to cells. In vivo experiments showed that the oHA-VES / F68-DTX polymer micelles were highly targeted. OHA-VES was an effective carrier for the delivery of DTX to tumor cells.
【学位授予单位】：佳木斯大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943
本文编号：2231431
[Abstract]:Aim to synthesize and characterize amphiphilic block polymer oligomeric polyhyaluronic acid-vitamin E succinate (oHAVES),) to prepare mixed polymer micelles containing docetaxel (oHA-VES/F68) and investigate their physicochemical properties and evaluate HAVES/F68-DTX in vitro and in vivo. Methods Amphiphilic block polymer carrier material was synthesized by the reaction of hyaluronic acid (oHA) with vitamin E succinate (VES). OHA-VES/F68 mixed polymer micelles were prepared by ultrasonic method. The morphology, particle size and Zeta potential, entrapment efficiency, drug loading and in vitro release of oHA-VES/F68 were investigated. The critical micelle concentration (CMC).) of the polymer was investigated by pyrene fluorescence probe method. The morphology, particle size and Zeta potential of polymer micelles were characterized by transmission electron microscope (TEM),) Ma Erwen dynamic light scattering particle size analyzer and dialyzed method. The synthesis of oHA-VES was identified by IR (FTIR) and 1H NMR. The cytotoxicity of MCF-7 cells was investigated by MTT assay. The fluorescence intensity of polymer micelles in mice after 24 hours was measured by in vivo imaging technique using DiR dye as fluorescence probe. Results oHA-VES polymer carrier materials were synthesized by amidation reaction, and oHAVES/F68 mixed polymer micelles were prepared by ultrasonic method. The particle size potential, encapsulation efficiency and drug loading of oHA-VES/F68-DTX were (91.2 卤7.51) nm, (-10.4 卤0.47) mV, (80.36 卤1.54) and (2.69 卤0.26), respectively. Under transmission electron microscope, the particles of oHA-VES/F68-DTX were spherical and round in shape. The cumulative release rate of DTX for 72 h was determined by 80.74%.CCK-8 method. The IC50 value of DTX to MCF-7 cells was 9.7 渭 g mL-1,oHA-VES/F68-DTX. There was no cytotoxicity in the blank carrier of DTX HA-VES. In vivo imaging showed that the polymer micelles of OHA-VES / F68 could significantly improve the targeting of polymer micelles in vivo. Conclusion the oHA-VES/F68-DTX polymer micelles were successfully prepared by ultrasonic method, and the preparation method is simple and feasible. The particle size and encapsulation efficiency of oHA-VES/F68-DTX with certain slow release properties were better. In vitro cell experiments showed that OHA-VES / F68-DTX had obvious cytotoxicity to cells. In vivo experiments showed that the oHA-VES / F68-DTX polymer micelles were highly targeted. OHA-VES was an effective carrier for the delivery of DTX to tumor cells.
【学位授予单位】：佳木斯大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R943
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