冰片修饰多烯紫杉醇/粉防己碱胶束处方优选及体外抗肿瘤作用  

Prescription Optimization of Bingpian(Borneolum Syntheticum)Modified Docetaxel/Tetrandrine Micelles and Its Antitumor Effect In Vitro

作　　者：刘洋[1] 司佳奇 蔡佳雨 刘婉滢 李沣芮 孔亮[1,2] 李学涛[1] LIU Yang;SI Jiaqi;CAI Jiayu;LIU Wanying;LI Fengrui;KONG Liang;LI Xuetao(College of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116600,Liaoning,China;Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications,Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600 [2]辽宁中医药大学,中医脏象理论及应用教育部重点实验室,辽宁沈阳110847

出　　处：《辽宁中医药大学学报》2023年第7期40-44,F0003,共6页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81874347);辽宁中医药大学中医脏象理论及应用教育部重点实验室开放基金项目(Nzyzx2102)。

摘　　要：目的 优化冰片修饰多烯紫杉醇/粉防己碱胶束的处方,考察其对鼠源脑胶质瘤细胞(C6)的体外毒性和对小鼠脑微血管内皮细胞(bEnd.3)体外靶向能力。方法 采用薄膜水化法构建冰片修饰多烯紫杉醇/粉防己碱胶束。Box-Behnken响应面法优化处方中影响包封率的3个因素[聚乙二醇1000维生素E琥珀酸酯(TPGS1000)/总药量、聚乙烯己内酰胺-聚乙酸乙烯酯聚乙二醇接枝共聚物(Soluplus)、水化温度],高效液相色谱法对冰片修饰多烯紫杉醇/粉防己碱胶束中多烯紫杉醇与粉防己碱进行含量测定。体外考察不同胶束对C6细胞存活率的影响。采用荧光显微镜法考察不同胶束对bEnd.3细胞的主动靶向性。结果 优选后的处方为Soluplus 80 mg、TPGS100040 mg、多烯紫杉醇0.8 mg、粉防己碱3.2 mg,处方量为5 mL。冰片修饰多烯紫杉醇/粉防己碱胶束中多烯紫杉醇和粉防己碱的平均包封率为93.20%±0.35%和92.38%±0.08%。空白靶向胶束对C6细胞生长无显著影响;冰片修饰多烯紫杉醇/粉防己碱胶束能明显抑制C6细胞生长。细胞摄取实验显示,经冰片修饰的胶束摄取量显著提高。结论该实验成功优化用于制备冰片修饰多烯紫杉醇/粉防己碱胶束的处方,经冰片修饰的多烯紫杉醇/粉防己碱胶束,细胞毒性强于多烯紫杉醇胶束,对bEnd.3细胞有良好的主动靶向性。Objective The formulation of Bingpian(Borneolum Syntheticum)modified docetaxel/tetrandrine micelles was optimized,toxicity to murine glioma cells(C6)in vitro and targeting ability to murine brain microvascular endothelial cells(bEnd.3)were investigated in vitro.Methods Bingpian(Borneolum Syntheticum)modified docetaxel/tetrandrine micelles were constructed by thin film hydration method.Three factors[D-alpha-tocopheroyl polyethylene glycol 1000 succinate(TPGS1000)/total dosage,polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer(soluplus),hydration temperature]affecting encapsulation rate were optimized in Box-Behnken response surface method optimization prescription.Docetaxel and tetrandrine in Bingpian(Borneolum Syntheticum)modified docetaxel/tetrandrine micelles were determined by HPLC.The effects of different micelles on the survival rates of C6 cells were investigated in vitro.The active targeting of different micelles to bEnd.3 cells was investigated by fluorescence microscopy.Results The optimized prescription was soluplus 80 mg,TPGS100040 mg,docetaxel 0.8 mg,tetrandrine 3.2 mg,in 5 mL.The average encapsulation rates of docetaxel and tetrandrine in Bingpian(Borneolum Syntheticum)modified docetaxel/tetrandrine micelles were(93.86%±0.57%)and(92.38%±0.08%).Blank targeted micelles had no significant effect on the growth of C6 cells.Bingpian(Borneolum Syntheticum)modified docetaxel/tetrandrine micelles could significantly inhibit the growth of C6 cells.Cell uptake experiments showed that the uptake of Bingpian(Borneolum Syntheticum)modified micelles was significantly improved.Conclusion This experiment successfully optimized the formulation of borneol modified polyene paclitaxel/tetrandrine micelles.The cytotoxicity of docetaxel/tetrandrine micelles modified by Bingpian(Borneolum Syntheticum)was stronger than docetaxel micelles,and had good effects on bEnd.3 cells active targeting.

关 键 词：冰片 多烯紫杉醇 粉防己碱 处方优选 细胞毒性 主动靶向性 

分 类 号：R285[医药卫生—中药学]