载吉西他滨介孔二氧化硅纳米粒的制备及其抗肿瘤活性评价

Preparation and Anti-cancer Activity Assessment of Gemcitabine Loaded Mesoporous Silica Nanoparticles

关键词:  吉西他滨  介孔二氧化硅纳米粒  抗肿瘤活性  体外释放

Key words:  gemcitabine  mesoporous silica nanoparticles  antitumor activity  in vitro release

摘要:

目的 制备载吉西他滨（gemcitabine，GemC）的介孔二氧化硅纳米粒（mesoporous silica nanoparticles，MSN），并对其体内外抗肿瘤活性进行评价。方法 采用聚合法制备GemC-MSN，采用激光粒度仪测定纳米粒的粒度分布和电位，并通过透射电镜对纳米粒的形态进行表征。应用UV评价纳米粒的载药量、包封率及体外释放特性。采用MTT染色法考察GemC-MSN对A549细胞的体外细胞毒性。建立体内肿瘤动物模型，评价纳米粒的体内抗肿瘤活性。结果 纳米粒分布均一，平均粒径为107.29 nm，PDI为0.167，Zeta电位为0.107 mV；药物的载药量和包封率分别为（37.31±1.25）%和（87.37±2.12）%；体外释放结果显示，纳米粒具有一定的缓释作用，96 h时释放达到平衡；体内外抗肿瘤试验结果表明，GemC-MSN较游离GemC具有更强的抗肿瘤活性。结论 MSN作为药物的新型载体，具有良好的生物相容性，并能显著提高GemC的载药量，控制药物的缓慢释放，能显著提高GemC的体内外抗肿瘤活性，将为GemC新型给药系统的深入研究提供参考。

Abstract:

OBJECTIVE To prepare carrier gemcitabine(GemC) mesoporous silica nanoparticles(MSN) and investigate its anti-tumor activities in vitro and in vivo. METHODS Polymerization method was applied to prepare GemC-MSN. Laser particle size analyzer was used to detect the particle size distribution and Zeta potential of nanoparticles. Morphology characterization of nanoparticles was analyzed by the transmission electron microscopy. And UV was applied to evaluate the drug loading, encapsulation efficiency and in vitro release rate. MTT staining was applied to study the cytotoxicity of GemC-MSN on A549 cells. RESULTS The nanoparticles were evenly distributed. The average particle diameter was 107.29 nm (PDI 0.167), and Zeta potential was 0.107 mV. The drug loading and encapsulation efficiency were (37.31±1.25)% and (87.37±2.12)%, individually. The in vitro release trial revealed that drug sustainedly released from the nanoparticles, reaching the balance within 96 h. Both of the in vitro and in vivo anti-tumor activities studies showed that GemC-MSN had a stronger anti-tumor activity than free GemC. CONCLUSION As a new carrier of drug, MSN displays the good biocompatibility. It can significantly improve the drug loading of GemC and control the release at a relative slow rate, increasing the anti-tumor activity of GemC in vitro and in vivo. This study can provide a reference for the futher investigation of GemC new drug delivery systems.