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[摘要]
目的 制备和厚朴酚脂质体(HK-Lipsomes),探讨其对小鼠乳腺癌细胞(4T1细胞)的体内外生长抑制作用。方法 将蛋黄卵磷脂、胆固醇、mPEG2000-DSPE2000、和厚朴酚按照质量比3:1:1:1,以注入法制备成和厚朴酚脂质体。通过Zetasizer nano ZS测定和厚朴酚脂质体的粒径,透射电镜观察和厚朴酚脂质体的形态。用噻唑蓝(MTT)比色法评价和厚朴酚脂质体对4T1细胞的细胞毒性。建立小鼠4T1乳腺癌肿瘤模型,以紫杉醇注射液为阳性对照,考察腹腔给药后和厚朴酚脂质体对肿瘤的抑制作用。结果 制备得到的和厚朴酚脂质体的平均粒径为(113.8±0.2)nm,多分散指数(0.209±0.005),电位为(-30.7±2.4)mV,透射电镜观察和厚朴酚脂质体为球型。和厚朴酚溶液和脂质体对4T1细胞的IC50值分别为(43.74±2.38)μg/mL和(12.52±2.24)μg/mL。和厚朴酚脂质体高(60 mg/kg)、中(40 mg/kg)、低(20 mg/kg)剂量组的抑瘤率分别为85.19%、60.95%和37.83%,呈剂量相关性。结论 实验使用较为简便的制备方法成功制备粒径较小、包封率高的和厚朴酚脂质体。荷瘤小鼠体内实验显示抑瘤效果良好。
[Key word]
[Abstract]
Objective To prepare honokiol liposomes (HK Liposomes) and explore their inhibition of breast cancer cells (4T1) in vitro and in vivo. Method The HK Liposomes were prepared by ethanol injection method using egg yolk lecithin, cholesterol, mPEG2000-DSPE2000 and honokiol (3:1:1:1, weight ratio) in formulation. The size of HK liposomes was determined by Zetasizer nano ZS. The morphology of HK Liposomes was observed by transmission electron microscope. MTT assay was used to evaluate the cytotoxic activity of HK liposomes against 4T1 murine breast cancer cell line with free HK as a control. The in vivo antitumor effect of the resultant HK Liposomes (ip administration) was evaluated on 4T1-bearing mice at different dose using PTX injection as a positive control. Results The HK liposomes were (113.8±0.209) nm in average particle size with smooth surface and spherical shape. The polydispersity index (PDI) value was (0.209±0.005) and zeta potential was (-30.7±2.4) mV. Honokiol liposomes showed significant higher cytotoxicity than free HK against 4T1 cells (IC50 value 12.52 μg/mL vs 43.74 μg/mL, P<0.01). On 4T1 tumor-bearing mice models, HK liposomes demonstrated a dose-dependent tumor suppression effect with inhibitory rate being 37.83%, 60.95% and 85.19% respectively for low (20 mg/kg), middle (40 mg/kg), and high dose (60 mg/kg). Conclusion In contrast, HK liposomes were successfully prepared with high encapsulation efficiency (94%), small particle size (113.8 nm) and demonstrated enhanced in vitro and in vivo anti-tumor efficacy in comparison with free HK.
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