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目的构建一种新型的药物传递系统——促黄体素释放素类似物靶向脂质体(LHRHa-Lipo),研究其体外靶向性及细胞毒性。方法采用薄膜超声法和生物素-链霉亲和素桥接法制备LHRHa-Lipo,采用激光粒度分析仪及透射电镜对该脂质体特质进行表征;以香豆素6为荧光探针,激光共聚焦显微镜检测卵巢癌细胞对载香豆素6的LHRHa-Lipo(LHRHa-Lipo-Cou6)与载香豆素6的普通脂质体(Lipo-Cou6)的摄取;MTT法检测细胞活力。结果制备的LHRHa-Lipo粒径(165.9±8.9)nm,Zeta电位为-(35.45±1.60)mV,形态圆整,包封率(90.8±3.1)%。经过相同时间孵育,A2780/DDP细胞摄取LHRHa-Lipo-Cou6量高于Lipo-Cou6(P<0.05),但SKOV3细胞对两种脂质体的摄取无明显差异(P>0.05)。A2780/DDP细胞与LHRHa-Lipo作用后细胞活力高于90%。结论采用薄膜超声法成功制备了LHRHa-Lipo,其靶向性和低毒性成为治疗卵巢癌一个有前景的药物传递系统。
OBJECTIVE: To construct a new drug delivery system, LHRHa-Lipo, to study its in vitro targeting and cytotoxicity. Methods LHRHa-Lipo was prepared by thin-film ultrasound and biotin-streptavidin bridging. The liposomes were characterized by laser particle size analyzer and transmission electron microscopy. Coumarin 6 The uptake of LHRHa-Lipo (LHRHa-Lipo-Cou6) and coumarin 6-containing liposomes (Lipo-Cou6) in ovarian cancer cells by confocal microscopy was tested by MTT assay. Results The diameter of LHRHa-Lipo was (165.9 ± 8.9) nm and its zeta potential was (-) - (35.45 ± 1.60) mV. After incubation at the same time, the amount of LHRHa-Lipo-Cou6 uptake in A2780 / DDP cells was higher than that in Lipo-Cou6 (P <0.05), but there was no significant difference in the uptake of the two liposomes between SKOV3 cells (P> 0.05). A2780 / DDP cells and LHRHa-Lipo cell viability higher than 90%. Conclusion LHRHa-Lipo was successfully prepared by thin-film sonography. Its targeting and low toxicity have become a promising drug delivery system for ovarian cancer.