目的 制备转铁蛋白（transferrin，Tf）修饰的雷公藤甲素（triptolide，TP）脂质体（Tf-TP@Lip），并对其进行质量评价和体外靶向性研究。方法 采用薄膜分散法制备Tf-TP@Lip，以包封率和载药量为考察指标，通过单因素考察和星点设计-效应面优化法筛选处方和最佳制备工艺；采用超滤离心法测定药物包封率；透射电子显微镜（TEM）观察脂质体微观形态；激光粒度仪测定脂质体的粒径、多分散指数（polydispersity index，PDI）和Zeta电位；并对其体外释放情况进行考察；采用流式细胞仪和荧光显微镜探究细胞摄取情况。结果 优化后Tf-TP@Lip的处方和工艺：脂药比为5.72∶1，脂胆比为8.11∶1，磷脂与DSPE-PEG₂₀₀₀的质量比为6∶1，成膜溶剂为无水乙醇，成膜温度60 ℃。制得的Tf-TP@Lip平均粒径为 （130.33±1.89）nm，PDI为0.19±0.03，Zeta电位为（−23.20±0.64）mV，包封率和载药量分别为（85.33±0.41）%和 （9.96±0.21）%，TEM下呈球形，大小均匀、圆整。体外释放研究表明，Tf-TP@Lip相比游离TP具有一定缓释效果。与非靶向雷公藤甲素脂质体（TP@Lip）相比，转铁蛋白的修饰明显增加了SMMC-7721对脂质体的摄取效率。结论 制备Tf-TP@Lip稳定、可行，粒径小、外观圆整且具备较高的包封率和载药量，可用于进一步的实验研究。

Objective To prepare transferrin (Tf) modified triptolide (TP) liposome (Tf-TP@Lip) and evaluate the quality and in vitro targeting. Methods The Tf-TP@Lip were prepared by thin-film dispersion method. With encapsulation efficiency and drug loading as indicators, single factor experiments and CCD-RSM were used to optimized the formulation and optimum preparation of Tf-TP@Lip; The drug entrapment efficiency was determined by ultrafiltration centrifugation; And the microscopic morphology of liposomes were observed under the transmission electron microscope (TEM); The particle size, polydispersion index (PDI), and Zeta potential were determined by laser particle size analyzer, and investigating the in vitro release of liposomes; flow cytometry and microscope were utilized for exploring the cellular uptake. Results The optimized preparation process and formulation were as follow: lipid /drug ratio was 5.72:1, lipid/cholesterol ratio was 8.11:1, the mass ratio of phospholipid to DSPE-PEG₂₀₀₀ was 6:1, the film-forming solvent was absolute ethanol and the temperature was 60 ℃. The mean particle size, PDI and Zeta potential of optimized TP@Lip were (130.33 ± 1.89) nm, 0.19 ± 0.03, (−23.2 ± 0.64) mV, respectively. The encapsulation efficiency and drug loading were (85.33 ± 0.41)% and (9.96 ± 0.21)%, respectively. The resulting liposomes exhibited spherical shape and were narrow in size distribution. The in vitro release studies showed that Tf-TP@Lip has sustained-release effect compared with free TP. And in contrast of non targeted triptolide liposomes (TP@Lip), Tf modification significantly increased the uptake efficiency of liposomes by SMMC-7721. Conclusion The preparation is stable and feasible, the obtained liposomes have a uniform particle size, round appearance and high encapsulation efficiency and drug loading, which can be used for further research.

R283.6

国家自然科学基金青年基金项目（81102815）