9-硝基喜树碱磷脂/胆盐混合胶束的制备及其性质研究  

Preparation and characterization of 9-nitrocamptothecin incorporated in egg phasphatidylcboline-sodium deoxycholate mixed micelles

作　　者：黄蕊[1] 龚涛[1] 张志荣[1] 

机构地区：[1]四川大学华西药学院靶向药物与释药系统教育部重点实验室,四川成都610041

出　　处：《华西药学杂志》2013年第2期117-120,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的制备9-硝基喜树碱磷脂/胆盐混合胶束(9-NC MMs),进行单因素处方筛选及初步性质研究。方法采用共沉淀法制备9-NC MMs;通过单因素考察,研究蛋黄卵磷脂(EPC)/脱氧胆酸钠(SDC)比例、辅料总浓度、水化介质离子强度对9-NC在混合胶束中溶解度的影响及抗氧剂叔丁基羟基茴香醚(BHA)用量筛选;拟定处方,考察9-NC MMs的粒径、形态、稀释稳定性和溶血性。结果 9-NC MMs优化处方为:EPC/(EPC+SDC)为0.4;辅料总浓度为2.5%;水化介质为0.9%NaCl溶液,BHA用量为0.005%。在此处方下,9-NC在水中的溶解度可提高到1 mg.mL-1;9-NC MMs具有良好的稀释稳定性,载药胶束平均粒径为7.04 nm,透射电镜说明胶束形态为均匀类圆形,无溶血作用。结论 9-NC EPC/SDC MMs的制备工艺简便,能有效提高9-NC溶解度,粒径分布理想、稳定性好、安全性好,便于临床静脉注射的应用。OBJECTIVE To prepare and characterize 9 - nitrocamptothecin incorporated egg phasphatidylcboline - sodium deoxy- cholate mixed micelles （9 -NC EPC/SDC MMs）. METHODS 9 -nitrocamptothecin mixed micelles （9 -NC MMs） were prepared using the co - precipitation method. A optimized formulation was obtained by single - factor method, which was used to study the effect of several factors on the water solubility of 9 - NC in MMs, including EPC/SDC ratio, total EPC/SDC concentration, ionic strength. The dosage of butylated hydroxyanisole （BHA） as antioxidant in formulation was also determined. Then the obtained 9 - NC MMs was characterized by investigation of physical compatibility, particle size distribution, morphology and hemolysis. RESULTS The opti- mized formulation of 9 - NC MMs was determined. The EPC/（ EPC ＋ SDC） ratio was 0.4. The total EPC/SDC concentration was 5% , 0.9% of NaCI was used to disperse the 9 - NC MMs and BHA with a concentration of 0. 005% was applied as antioxidant. This formu- lation enhanced the water solubility of 9 -NC to 1 mg. mL-t, and was physically compatible with injection solutions. The drug loaded MMs had an average size of 7.04 nm and a round shape was observed by transmission electron microscope （TEM）. Moreover, no hemolysis effect of 9 -NC MMs was detected. CONCLUSION 9 -NC EPC/SDC MMs,prepared by simple and convenient method, significantly enhanced the water solubility of 9 - NC, and had improved size distribution, stability and safety, thus could be used for intravenous injection in clinic.

关 键 词：9-硝基喜树碱 胆盐 磷脂 混合胶束 溶解度 

分 类 号：R94[医药卫生—药剂学]