[关键词]
[摘要]
目的 制备D-α-维生素E聚乙二醇1000琥珀酸酯(TPGs)修饰的雷公藤甲素固体脂质纳米粒(TPGs-Tri-SLNs),并评价其质量。方法 采用热熔乳化-超声法制备TPGs-Tri-SLNs,并以山嵛酸甘油酯浓度(X1),大豆磷脂与TPGs比例(X2)和山嵛酸甘油酯与药物比例(X3)作为考察因素,以TPGs-Tri-SLNs的粒径分布(Y1)和药物包封率(Y2)作为评价指标,通过中心复合设计-效应面法优化TPGs-Tri-SLNs的处方,粒度分析仪测定其粒径分布,透射电镜观察其微观形态,并考察了TPGs-Tri-SLNs的体外药物释放特性。结果 TPGs-Tri-SLNs的最佳处方组成为:山嵛酸甘油酯浓度为10%,大豆磷脂与TPGs比例4:1,山嵛酸甘油酯与药物比例为60:1,按照最优处方制备3批TPGs-Tri-SLNs的平均粒径为(107.8±16.9)nm,包封率为91.4%±1.1%;在透射电镜下可以观察到TPGs-Tri-SLNs呈球型分布,表面光滑;TPGs-Tri-SLNs在前4 h内药物释放较快,后期释药速率较为平稳,24 h药物释放可以达到85%。结论 通过中心复合设计-效应面法优化并得到TPGs-Tri-SLNs的最优处方,处方设计合理,制备工艺简单。
[Key word]
[Abstract]
Objective To prepare D-α-vitamin E polyethylene glycol 1000 succinate (TPGs) modified triptolide solid lipid nanoparticles (TPGs-Tri-SLNs) and evaluate their quality. Methods TPGs-Tri-SLNs were prepared by hot melt emulsificationultrasonic method, and the concentration of Compritol-888 ATO (X1), the ratio of soybean phospholipid to TPGs (X2) and the ratio of Compritol-888 ATO to triptolide (X3) were used as the investigation factors, the particle size distribution (Y1) and encapsulation efficiency (Y2) of TPGs-Tri-SLNs were used as evaluation indexes, and the formulation of TPGs-Tri-SLNs was optimized by central composite design-response surface methodology (CCD-RSM). The particle size distribution of TPGs-Tri-SLNs were determined by particle size analyzer. The microscopic morphology was observed by transmission electron microscopy, and the in vitro drug release characteristics of TPGs-Tri-SLNs were investigated. Results The optimal formulation of TPGs-Tri-SLNs as follows:Compritol-888 ATO concentration was 10%, the ratio of soybean phospholipid to TPGs was 4:1, the ratio of Compritol-888 ATO to triptolide was 60:1. Three batches of TPGs-Tri-SLNs were prepared according to the optimal formulation. The average particle size was (107.8±16.9) nm and the encapsulation efficiency was 91.4%±1.1%. Under the transmission electron microscope, TPGs-Tri-SLNs could be observed to have a spherical distribution with a smooth surface. The drug release of TPGs-Tri-SLNs showed a bursting in the first 4 h, while it was slow and stable in the later stage, and the drug release in 24 h could reach 85%. Conclusion This study used central composite design-response surface methodology optimization and obtained the optimal formulation of TPGs-Tri-SLNs. The formulation design was reasonable and the preparation process was simple, which could be further investigated.
[中图分类号]
R927.11
[基金项目]