冰片修饰五味子乙素胶束处方优选及体外对bEnd.3细胞靶向性评价研究  

Formulation Optimization of Bingpian(Borneol)Modified Schisandrin B Micelles and Their Effect on Targeting Evaluation in Vitro of bEnd.3 Cell

作　　者：李沣芮 刘洋[1] 司佳奇 刘婉滢 蔡佳雨 孔亮[1] 李学涛[1] 程岚[1] LI Fengrui;LIU Yang;SI Jiaqi;LIU Wanying;CAI Jiayu;KONG Liang;LI Xuetao;CHENG Lan(College of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116600,Liaoning,China)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600

出　　处：《中华中医药学刊》2024年第2期245-249,I0036,I0037,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：辽宁省自然科学基金项目(2019-MS-226);辽宁中医药大学自然科学项目(2021LZY009)。

摘　　要：目的优化冰片修饰五味子乙素胶束(Borneol-Schisandrin B-Micelles,Bor-Sch B-Ms)处方,并对其体外脑靶向作用进行初步探索。方法采用薄膜分散法制备Bor-Sch B-Ms;对Soluplus/TPGS1000质量比(mg/mg)、Soluplus/五味子乙素质量比(mg/mg)和水化温度(℃)进行优化,确定Bor-Sch B-Ms的最优处方制备工艺;并对最优处方工艺制得的胶束进行表征;采用高效液相色谱法(HPLC)对胶束中五味子乙素进行含量测定,以测得Bor-Sch B-Ms的包封率;利用不同药物对小鼠脑内血管内皮细胞(bEnd.3)的荧光摄取实验进行Bor-Sch B-Ms体外靶向性评价。结果最优处方为Soluplus 120 mg,Soluplus/TPGS1000=2∶1,Soluplus/五味子乙素=12∶1,DSPE-PEG20002 mg,水化温度40℃,处方量为5 mL。所得最优胶束的粒径为(93.72±0.65)nm,电位为(-2.73±0.35)mV,Bor-Sch B-Ms的包封率为(93.54±0.86)%。体外细胞摄取实验显示,与五味子乙素胶束组(Sch B-Ms)相比,Bor-Sch B-Ms组细胞的荧光强度明显增加(P<0.05)。结论通过Box-Behnken设计-响应面法确定Bor-Sch B-Ms最优处方,制备得到的Bor-Sch B-Ms具有潜在的脑靶向性。Objective To optimize the formulation of Bingpian(Borneol)modified Schisandrin B micelles(Borneol-Schisandrin B-Micelles,Bor-Sch B-Ms)and preliminarily evaluate their brain targeting effect in vitro.Methods Bor-Sch B-Ms were prepared by thin film dispersion method.The three factors of Soluplus/TPGS1000mass ratio(mg/mg),Soluplus/Schisandrin B mass ratio(mg/mg)and hydration temperature(℃)were investigated.The optimal formulation and preparation process of Bor-Sch B-Ms were determined by Box-Behnken design response surface method,and the micelles prepared by the optimal formulation process were characterized.The content of Schisandrin B in micelles was determined by high performance liquid chromatography(HPLC)to measure the entrapment efficiency of Bor-Sch B-Ms.The targeting ability of Bor-Sch B-Ms in vitro was appraised by the fluorescence uptake experiment of different medications on the vascular endothelial cells(bEnd.3)in the mouse brain.Results The first-best prescription was Soluplus 120 mg,Soluplus/TPGS1000=2∶1,Soluplus/Schisandrin B=12∶1,DSPE-PEG20002 mg,hydration temperature 40℃and prescription dosage 5 mL.The particle size of the optimal micelles was(93.72±0.65)nm,the potential was(-2.73±0.35)mv,and the entrapment efficiency of Bor-Sch B-Ms was(93.54±0.86)%.In vitro cell uptake experiment showed that the fluorescence intensity of cells in Bor-Sch B-Ms group was significantly higher than that in Sch B-Ms group(P<0.05).Conclusion The first-best prescription of Bor-Sch B-Ms was screened by Box-Behnken design response surface method and the prepared Bor-Sch B-Ms have certain potential brain targeting.

关 键 词：五味子乙素 冰片 胶束 阿尔茨海默病 Box-Behnken响应面法 血脑屏障 

分 类 号：R284.1[医药卫生—中药学]