基于Box-Behnken实验优化地榆皂苷元固体脂质纳米粒的制备  

Preparation and optimization of Burnet sapogenin loading solid lipid nanoparticle by u-sing Box-Behnken design

作　　者：代良敏 代良萍 陈永钧 杨明 黄群莲 DAI Liang-min;DAI Liang-ping;CHEN Yong-jun;YANG Ming;HUANG Qun-lian(Affiliated Hospital of Southwest Medical University,Luzhou 646000,China;State Key Laboratory of Innovation Drug and Efficient Energy-Saving Pharmaceutical Equipment,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]西南医科大学附属医院,四川泸州646000 [2]江西中医药大学创新药物与高效节能降耗制药设备国家重点实验室,江西南昌330004

出　　处：《时珍国医国药》2023年第9期2117-2120,共4页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81373976);国家新药创制重大专项(2013ZX09103002-013)。

摘　　要：目的基于Box-Behnken实验设计探讨优选地榆皂苷元固体脂质纳米粒(BS-SLN)的处方。方法采用BS-SLN中以BS为含测指标,以包封率与载药量为指标,在单因素考察的基础上,利用3因素3水平Box-Behnken实验设计,考察脂药比(总脂质与BS的质量比)(X1)、卵磷脂-硬脂酸投料比(质量比,X2)、磷酸盐缓冲液(PBS,pH 7.4)的质量分数(X3)对SLN包封率(Y1)、载药量(Y2)和总评归一值(OD)的影响,通过建立相应的二项式数学模型优化处方。优化后得到的BS-SLN通过透射电镜观察其形态;对其粒度的测定、Zeta电位的测定及pH值进行测定;采用平衡透析法进行BS-SLN的释放度测定。结果优选的处方工艺为脂药比为7.5∶1,卵磷脂-硬脂酸投料比为10∶1,PBS质量分数为3%。制备的BS-SLN透射电镜下呈球形或椭圆球形,平均粒径为(178.8±32.1)nm,包封率为(83.54±0.54)%,载药量为(11.56±0.61)%。48 h体外累积释放率达82.13%。结论BS-SLN稳定性良好,体外释放性能良好,具有缓释特性。Objective To apply Box-Behnken design to investigate main and interaction effects of formulation parameters in op-timizing solid lipid nanoparticle of Burnet sapogenin formulation.Methods BS-SLN with BS as the measured indicators,Burnet sapogenin solid lipid nanoparticles was prepared by film dispersion method,based on the single single-factor experiment,a three-factor,three-level Box-Behnken experimental design was employed to construct a second order polynomial equation for the optimized procedure,with the amount of lipid ratio(total lipid and BS mass ratio)(X1),Lecithin/weight ratio stearic acid(X2),and the concentration of the PBS(pH 7.4)(X3)as the independent variables and the entrapment efficiency(Y1),drug loading(Y2)and OD(Y3)as the response variables.The optimized BS-SLN was observed by transmission electron microscopy(TEM).The determination of the particle size,the determination of Zeta potential and the pH value were carried out.The release of BS-SLN was determined by equilibrium dialysis method.Results The best formulation process was as following:The lipid ra-tio was 7.5:1,lecithin/stearic acid weight ratio of 10:1,PBS concentration was 3%.These prepared nanoparticles showed spherical or ellipsoidal under transmission electron microscope,average particle size,encapsulation efficiency and drug loading were(178.8±32.1)nm,(83.54±0.54)%and(11.56±0.61)%,respectively;release was 82.13%at 48 h,particle size and encapsulation efficiency had no significant change in 30 d.Conclusion BS-SLN has good stability,good in vitro re-lease and stability with excellent antitumor activity.

关 键 词：地榆皂苷元 脂质纳米粒 BOX-BEHNKEN设计 包封率 载药量 累积释放率 脂药比 处方工艺 

分 类 号：R284.2[医药卫生—中药学]