槲皮素PLGA-TPGS纳米粒的质量考察

Quality Investigation of Quercetin-loaded PLGA-TPGS Nanoparticles

目的以自制材料乳酸羟基乙酸共聚物-维生素E聚乙二醇1000琥珀酸酯(PLGA-TPGS)和市售材料乳酸羟基乙酸共聚物(PLGA)为载体分别制备槲皮素PLGA-TPGS纳米粒(QPTN)和槲皮素PLGA纳米粒(QPN),体外考察和比较2种纳米粒的质量。方法应用超声乳化-溶剂挥发法分别制备QPTN和QPN,并用透射电子显微镜和激光粒度仪测定2种纳米粒的外观、粒径和表面电荷。采用反相高效液相色谱(RP-HPLC)法,色谱柱为Hypersil C18(4.6 mm×250 mm,5μm)、甲醇-0.03%磷酸溶液(3∶2)为流动相,检测波长为370 nm,测定2种纳米粒的载药量、包封率和体外释放度,对二者的质量进行体外考察和比较。结果 QPTN和QPN的粒径分别为(155.4±2.7)和(363.8±3.2)nm,载药量和包封率分别为(21.6±2.8)%,(93.7±2.9)%和(15.0±1.5)%,(64.6±1.6)%(n=6)。体外药物释放显示2种纳米粒均有明显的缓释作用,30 d时QPTN和QPN的体外累积释放率分别为(85.8±2.8)%和(68.6±1.4)%(n=6)(P<0.05)。结论QPTN比QPN粒径相对更小、载药量和包封率更大,体外显示有明显的缓释作用,释放比QPN更快、更完全。

Objective To prepare quercetin （ QT ）-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate （ PLGA-TPGS） nanoparticles （ QPTN） and QT-loaded polylactic-co-glycolic acid （ PLGA） nanoparticles （ QPN） by using QT as model drug and PLGA-TPGS or PLGA as carrier materials, and to investigate the quality of the two nanoparticles. Methods QPTN and QPN were prepared by using the ultrasonic emulsification-solvent evaporation method, and their surface morphology,size and surface charge were detected by using a transmission electron microscope （ TEM） and a Nano ZS90 light scattering and laser Doppler anemometry, respectively. Drug loading （ DL） , entrapment efficiency （ EE） and in vitro drug release of QT in the two nanoparticles were determined by using a reverse phase-high performance liquid chromatography （RP-HPLC） on Hypersil C18 column （4.6 mm×250 mm, 5 μm） with methanol and 0.03% phosphoric acid （3︰2） as mobile phase, and the detective wavelength was 370 nm. Results TEM images exhibited that two nanoparticles were all spherical and regular. The average sizes of QPTN and QPN were （155.4±2.7） nm and （363.8±3.2） nm, while DL and EE of QPTN were approximately （21.6±2.8）%, （93.7±2.9）% （n=6）, and DL and EE of QPN were approximately （15.0±1.5）%, （64.6± 1.6）% （n=6）, respectively. Both of nanoparticles exhibited sustained release, and the cumulative QT release of QPTN and QPN reached （85.8±2.8）% and （68.6±1.4）% （n=6） at day 30, respectively, with a significant difference between them （P〈0.05） . Conclusion QPTN gets smaller size, higher DL and EE, and exhibits sustained release, and the in vitro cumulative QT release is faster and more complete than QPN relatively.