紫杉醇-油酸和鸦胆子油分子配型组装纳米乳给药系统研究  

Study on paclitaxel-oleic acid and Brucea javanica oil core-matched nanoemulsions drug delivery

作　　者：张宽云 马燕[1] 

机构地区：[1]广州中医药大学中药学院,广东广州510006

出　　处：《中草药》2017年第8期1544-1552,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81403109);广东省科技计划项目(2016A020217017);广东省卫生与计划生育委员会项目(A2015596)

摘　　要：目的优化紫杉醇-油酸(PTX-OA)和鸦胆子油(BJO)分子配型组装纳米乳给药系统(PTX-OA/BJO CMNEs)的处方及制备工艺。方法通过酯化反应制备得PTX-OA并建立检测PTX-OA的HPLC方法。采用超声乳化法制备PTX-OA/BJO CMNEs。单因素实验选出对PTX-OA/BJO CMNEs粒径影响较大的3个因素,L16(43)正交试验以这3个因素油相质量浓度(A)、聚山梨酯-80用量(B)和超声功率(C)为考察因素,以平均粒径为评价标准,优选PTX-OA/BJO CMNEs的处方及制备工艺。对优选条件制备的PTX-OA/BJO CMNEs进行制剂学评价及体外细胞毒实验。结果 HPLC法检测PTX-OA在5~25μg/m L线性关系良好,回归方程Y=12.709 X+6.252 0,r=0.999 5。最优处方为油相质量浓度为6.50 mg/m L,聚山梨酯-80-油相比例为3.5∶6.5,超声乳化功率为120 W。制备的PTX-OA/BJO CMNEs外观良好,平均包封率为(100.6±1.9)%,平均粒径(108.7±2.3)nm,多分散系数(PDI)为0.232±0.038。透射电子显微镜(TEM)形态观察表明PTX-OA/BJO CMNEs粒径接近100 nm,分布较均一;其体外释放度在48 h达到67%。PTX-OA/BJO CMNEs溶液置于4℃,避光环境下保存60d,包封率、粒径基本保持不变,稳定性较好。体外细胞毒实验显示,BJO与PTX-OA联用对Hep G-2细胞生长抑制具有一定的协同作用。结论优化后的PTX-OA/BJO CMNEs制备工艺简单易行,且药物之间具有增强细胞毒作用,为PTX和BJO联合用药的抗肿瘤作用机制的研究奠定了基础。Objective To optimize the preparation method of paclitaxel-oleic acid（PTX-OA）/Brucea javanica oil（BJO） corematched nanoemulsions（CMNEs）. Methods PTX-OA/BJO was synthesized by esterification of PTX and OA, and determined by HPLC. Ultrasionic emulsification was used to prepare the PTX-OA/BJO CMNEs. The concentration of oil phase（A）, quality of polysorbate 80（B）, and ultrasonic power（C） were selected as the significant factors after single-factor experiments and applied in L16（43） orthogonal array design with the average particle size as criterion. In addition, the physicochemical properties and cytotoxicity of PTX-OA/BJO CMNEs were tested. Results Linear range of PTX-OA was 5—25 μg/m L, Y = 12.709 X ＋ 6.252 0, r = 0.999 5. The optimized conditions of PTX-OA/BJO CMNEs were as follows： The concentration of oil phase was 6.50 mg/m L, the mass ratio of polysorbate 80 to oil phase was 3.5：6.5 and the ultrasonic power was 120 W. The CMNEs prepared by the optimal conditions showed an entrapment efficiency of（100.6 ± 1.9）% and the nanoscale particle size was（108.7 ± 2.3） nm, PDI was 0.232 ± 0.038. The morphology of CMNEs examined by TEM exhibited a uniform and spherical shape. In vitro drug release was up to 67% after 48 h. After PTX-OA/BJO CMNEs sealed in a bottle were stored at 4 ℃ for 60 h, the average particle size and entrapment efficiency had no significant change. The cytotoxicity in vitro showed that the combined PTX-OA/BJO CMNEs could obviously inhibit the proliferation of Hep G-2 cells. Conclusion The current study demonstrates the feasibility of incorporating PTX-OA and BJO into a single CMNEs for the synergism in cancer therapy. Furthermore, the preparation of PTX-OA/BJO CMNEs has the advantages of practicability and simple operation, as well lays the foundation for the further mechanism research of the combined paclitaxel and BJO in oncotherapy.

关 键 词：紫杉醇 鸦胆子油 分子配型组装纳米乳给药系统 正交试验 稳定性 超声乳化法 包封率 细胞毒作用 

分 类 号：R283.6[医药卫生—中药学]