基于TPGS的紫杉醇自微乳的制备及其评价  

Preparation and evaluation of TPGS-based self-microemulsifying drug delivery system of paclitaxel

作　　者：张璐茜 朱睿 孙懿 常聪 陈欣妍 ZHANG Lu-xi;ZHU Rui;SUN Yi;CHANG Cong;CHEN Xin-yan(Pharmacy Faculty,Hubei University of Chinese Medicine,Hubei Wuhan 430065,China)

机构地区：[1]湖北中医药大学药学院,湖北武汉430065

出　　处：《中国医院药学杂志》2023年第9期977-982,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的:制备基于P-糖蛋白抑制剂D-α-生育酚聚乙二醇琥珀酸酯(TPGS)的紫杉醇自微乳(PTX-T-SMEDDS),以增强耐药肿瘤细胞对PTX的敏感性。方法:采用伪三元相图法筛选TPGS自微乳(T-SME)的制备处方;以粒径、多分散指数(PDI)和PTX包封率为指标筛选PTX-T-SMEDDS的制备条件;利用马尔文粒径仪和透射电镜表征PTX-T-SMEDDS乳化后的粒径、Zeta电位、PDI和形态,并利用高效液相色谱(HPLC)测定药物包封率,考察PTX-T-SMEDDS的体外释药行为和稳定性;以非小细胞肺癌紫杉醇耐药株A549/Taxol为模型,采用MTT法评价细胞毒性。结果:T-SME的最终处方为维生素E 20%,TPGS 40%,异丁醇40%。在PTX与维生素E/TPGS/异丁醇的质量比为1∶120时制得PTX-T-SMEDDS,其乳化后的粒径为(20.64±0.23) nm,乳滴形态为类圆形,PTX包封率为(85.10±3.05)%。相较于游离PTX,PTX-T-SMEDDS呈缓慢释药行为。PTX-T-SMEDDS具有较好的贮存稳定性、稀释稳定性和离心稳定性。PTX-T-SMEDDS对A549/Taxol的IC_(50)为7.33μg·mL^(-1),约为游离PTX的1/4。结论:成功制备了PTX-T-SMEDDS,该自微乳可缓慢释放PTX,且具有一定的稳定性,可提高耐药细胞A549/Taxol对PTX的敏感性。OBJECTIVE To prepare self-microemulsifying drug delivery system of paclitaxel(PTX-T-SMEDDS)based on P-glycoprotein inhibitor D-α-tocopheryl polyethylene glycol succinate(TPGS),so as to enhance the sensitivity of drug-resistant tumor cells to PTX.METHODS The preparation formulation of TPGS-based self-microemulsion(T-SME)was screened by pseudo-ternary phase diagram method;the preparation process of PTX-T-SMEDDS was screened based on particle size,polydispersity index(PDI)and paclitaxel encapsulation rate;the particle size,Zeta potential,PDI and morphology of PTX-T-SMEDDS after emulsification were characterized by a Malvern particle size meter and a transmission electron microscope,and the drug encapsulation efficiency was investigated by high performance liquid chromatography(HPLC).The in vitro drug release behavior and stability of PTX-T-SMEDDS were evaluated;paclitaxel-resistant non-small cell lung cancer cell strain A549/Taxol was used as model to assess the cytotoxicity by MTT method.RESULTS The final formulation of T-SME was vitamin E 20%,TPGS 40%and iso-butanol 40%.PTX-T-SMEDDS was prepared when the mass ratio of PTX to vitamin E/TPGS/isobutanol was 1∶120.After emulsification,the particle size was(20.64±0.23)nm,the shape of the emulsion droplet was quasi-circular,and the encapsulation rate of PTX was(85.10±3.05)%.Compared with free PTX,PTX-T-SMEDDS presented a slow-release behavior,and had good storage stability,dilution stability and centrifugal stability.The IC50 of PTX-T-SMEDDS to A549/Taxol was 7.33μg·mL-1,which was about one fourth of that of free PTX.CONCLUSION TPGS-based self-microemulsifying drug delivery system of paclitaxel was successfully prepared,which can release PTX slowly with good stability,and more importantly,it can improve the sensitivity of drug-resistant tumor cell A549/Taxol to PTX.

关 键 词：紫杉醇 D-α-生育酚聚乙二醇琥珀酸酯 自微乳 体外释放 稳定性 

分 类 号：R943[医药卫生—药剂学]