Song Xiangrong, Zhao Yu, Hou Shixiang, Xu Fangyuan, Zhao Rongli, He Junyao, Cai Zheng, Li Yuanbo, Chen Qiuhong
West China School of Pharmacy, Sichuan University, Sichuan, PR China.
Eur J Pharm Biopharm. 2008 Jun;69(2):445-53. doi: 10.1016/j.ejpb.2008.01.013. Epub 2008 Jan 19.
PLGA nanoparticles simultaneously loaded with vincristine sulfate (VCR) and quercetin (QC) were prepared via O/W emulsion solvent evaporation. Six independent processing parameters and PLGA characteristics were assessed systematically to enhance the incorporation of the dual agents with different properties (VCR and QC, hydrophilic and hydrophobic molecule, respectively) into PLGA nanoparticles and control particle size. Approaches investigated for the enhancement of drug entrapment efficiencies and the controlling of particle size included the influence of the molecular weight (MW) of PLGA and the lactide-to-glycolide (L:G) ratio of PLGA, PLGA concentration, PVA concentration, initial QC content, acetone-to-dichloromethane (A/D) volume ratio, aqueous phase pH and aqueous to organic phase (W/O) volume ratio. The nanoparticles produced by optimal formulation were submicron size (139.5+/-4.3 nm, n=3) with low polydispersity index (0.095+/-0.031, n=3). Nanoparticles observed by transmission electron microscopy (TEM) showed extremely spherical shape. The entrapment efficiencies determined by high performance liquid chromatography (HPLC) by ultracentrifuge method were 92.84+/-3.37% for VCR and 32.66+/-2.92% for QC (n=3). The drug loadings were 0.0037+/-0.0001% for VCR and 1.36+/-0.12% for QC (n=3).
通过水包油乳液溶剂蒸发法制备了同时负载硫酸长春新碱(VCR)和槲皮素(QC)的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒。系统评估了六个独立的工艺参数和PLGA特性,以提高两种性质不同的药物(分别为亲水性分子VCR和疏水性分子QC)在PLGA纳米粒中的包封率并控制粒径。所研究的提高药物包封率和控制粒径的方法包括PLGA的分子量(MW)、PLGA的丙交酯与乙交酯比例(L:G)、PLGA浓度、聚乙烯醇(PVA)浓度、初始QC含量、丙酮与二氯甲烷体积比(A/D)、水相pH值以及水相与有机相体积比(W/O)的影响。通过优化配方制备的纳米粒尺寸为亚微米级(139.5±4.3 nm,n = 3),多分散指数较低(0.095±0.031,n = 3)。透射电子显微镜(TEM)观察到纳米粒呈极规则的球形。采用超速离心法通过高效液相色谱(HPLC)测定的包封率,VCR为92.84±3.37%,QC为32.66±2.92%(n = 3)。载药量VCR为0.0037±0.0001%,QC为1.36±0.12%(n = 3)。