多西他赛磷脂/胆盐复合胶束的制备及性质研究

Preparation and characterization of docetaxel incorporated in phosphatidylcholine-sodium desoxycholate mixed micelles

目的制备多西他赛磷脂/胆盐复合胶束(DOX MMs)并进行处方筛选及初步性质研究。方法以共沉淀法制备多西他赛磷脂胆盐复合胶束,利用高效液相色谱法考察不同条件(磷脂比例、辅料总浓度、pH值、离子强度)对多西他赛在复合胶束中溶解度的影响。通过激光粒度仪测定胶束的粒径分布和电位,透射电子显微镜测定胶束的表面形态,稀释实验考察胶束的稳定性。结果 DOX MMs优化处方中磷脂/总辅料比例为0.4;辅料总浓度为2.5%;水化介质为纯水。载药胶束平均粒径为18.56 nm,Zeta电位为-24.3 mV,胶束为类圆多边形,分布均匀。胶束具有较好的稀释稳定性。结论 DOX MMs的制备工艺简单,能有效提高多西他赛的溶解度,稳定性好,有望成为多西他赛的新型药物传递系统。

Objective To prepare and characterize docetaxel incorporated phosphatidylcholine-sodium desoxycholate mixed micelles（DOX EPC/SDC MMs）. Methods Docetaxel mixed micelles（DOX MMs） were prepared using the coprecipitation method. An optimized formulation was obtained by single factor method,which was used to study the effect of several factors on water solubility of DOX in MMs,including EPC/total（EPC ＋ SDC） concentration,total（EPC ＋ SDC）concentration,the pH and ionic strength of the hydrated solution. Then,the obtained DOX MMs were characterized by investigating particle size distribution and morphology,and by conducting dilute experiments to examin micelle stability.Results The EPC/total（EPC ＋ SDC） concentration ratio was 0. 4. The total supplementary material concentration was2. 5%. Pure water was used to disperse the film. The drug loaded MMs had an average size of 18. 56 nm and average zeta potential of- 24. 3 mV. A roundlike shape was observed under a transmission electron microscope（TEM）. Conclusion DOX EPC/SDC MMs,prepared by a simple and convenient method,can enhance water solubility,is physically compatible with injection solutions and is expected to become a new drug delivery system.