腫瘤靶向oHA-VES納米聚合物膠束載體的構(gòu)建與評價
發(fā)布時間：2018-09-08 19:10
【摘要】：目的合成并表征兩親性嵌段聚合物寡聚透明質(zhì)酸-維生素E琥珀酸酯(oHAVES),制備載多西他賽oHA-VES/F68混合聚合物膠束并考察其理化性質(zhì),并對HAVES/F68-DTX進(jìn)行體外和體內(nèi)的評價。方法將透明質(zhì)酸(oHA)與維生素E琥珀酸酯(VES)通過酰胺反應(yīng)合成兩親性嵌段聚合物載體材料。超聲法制備oHA-VES/F68混合聚合物膠束,對oHA-VES/F68的形態(tài)、粒徑、Zeta電位、包封率、載藥量和體外釋放進(jìn)行考察,通過芘熒光探針法考察聚合物的臨界膠束濃度值(CMC)。采用透射電鏡(TEM)、馬爾文動態(tài)光散射粒徑儀對聚合物膠束的形態(tài)、粒徑大小及Zeta電位進(jìn)行表征;采用透析法考察體外釋放。紅外法(FTIR)和核磁共振氫譜(1H NMR)鑒定oHA-VES的合成。采用MTT法考察MCF-7細(xì)胞的細(xì)胞毒性。以DiR染料作為熒光探針用荷瘤小鼠體內(nèi)活體成像技術(shù)測定聚合物膠束在24h后小鼠體內(nèi)的熒光強(qiáng)度。結(jié)果通過酰胺化反應(yīng)合成oHA-VES聚合物載體材料,采用超聲法制備oHAVES/F68混合聚合物合物膠束。所制得的oHA-VES/F68-DTX的粒徑、Zeta電位、包封率、載藥量分別為(91.2±7.51)nm,(-10.4±0.47)mV,(80.36±1.54)%,(2.69±0.26)%。透射電鏡下觀察oHA-VES/F68-DTX的粒子呈球形,形態(tài)圓整,分散均勻。72 h累積釋放率為80.74%。CCK-8法測定DTX對MCF-7細(xì)胞的IC50值為9.7μg·mL-1,oHA-VES/F68-DTX有較大的細(xì)胞毒性,oHA-VES空白載體基本無細(xì)胞毒性�；铙w成像表明,oHA-VES/F68聚合物膠束在體內(nèi)能夠顯著提高聚合物膠束的靶向性。結(jié)論通過超聲法成功制備了oHA-VES/F68-DTX聚合物膠束,所采用的制備方法簡便可行。具有一定緩釋性能的oHA-VES/F68-DTX的粒徑、包封率較好。體外細(xì)胞實驗表明,oHA-VES/F68-DTX對細(xì)胞有明顯的毒性作用。體內(nèi)試驗表明,oHA-VES/F68-DTX聚合物膠束具有顯著的靶向性。oHA-VES是一種可將DTX遞送到腫瘤細(xì)胞的有效的載體。
[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 鹵7.51) nm, (-10.4 鹵0.47) mV, (80.36 鹵1.54) and (2.69 鹵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.
【學(xué)位授予單位】：佳木斯大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R943
本文編號：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 鹵7.51) nm, (-10.4 鹵0.47) mV, (80.36 鹵1.54) and (2.69 鹵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.
【學(xué)位授予單位】：佳木斯大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R943
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