[关键词]
[摘要]
目的 制备地塞米松脂质体,探讨地塞米松对乳腺癌4T1细胞的生长抑制作用及对荷瘤鼠的抗肿瘤药效。方法 采用薄膜分散-超声法,以粒径和多分散指数(PDI)为指标进行单因素实验考察了大豆磷脂(SPC)与甲氧基聚乙二醇磷脂(DSPE-mPEG2000)的质量比、SPC与地塞米松的质量比、超声时间对地塞米松脂质体粒径的影响从而筛选得到最佳处方和最佳工艺条件。采用MTT法比较地塞米松注射液和地塞米松脂质体对4T1细胞的作用。建立4T1 BAL B/c荷瘤小鼠模型,研究地塞米松脂质体对4T1荷瘤小鼠的体内抗肿瘤作用。结果 当SPC与DSPE-mPEG2000质量比为5:1、SPC与地塞米松质量比为50:3、超声时间为20 min时制备得到的脂质体粒径最小,粒径分布最窄,室温放置15 d稳定,于生理介质中稳定。MTT测定结果显示地塞米松注射液和脂质体对4T1细胞生长抑制作用均较弱,但在4T1荷瘤鼠的体内实验中,在5 mg/kg的给药剂量下,地塞米松脂质体的抑瘤率却高达78.9%,显著高于地塞米松注射液(33.4%,P<0.05)和8 mg/kg紫杉醇注射液(55%,P<0.05)。结论 制备的地塞米松脂质体放置于生理介质中均能稳定存在,能口服能静脉给药。地塞米松脂质体对4T1荷瘤小鼠肿瘤生长有较强的抑制作用,但体外对4T1细胞抑制抑制作用并不强,推测地塞米松脂质体是通过调节肿瘤微环境来抑制肿瘤生长。
[Key word]
[Abstract]
Objective To prepare long-circulating dexamethasone liposomes and investigate its inhibitory effect on the growth of breast cancer 4T1 cells and its anti-tumor effect on tumor-bearing mice. Methods The film dispersion-ultrasonic method was used to conduct single-factor experiments with particle size and polydispersity index (PDI) as indicators to investigate the effect of mass ratio of SPC to DSPE-mPEG2000, mass ratio of SPC to dexamethasone and ultrasound time on particle size to screen for the best prescription and the best process conditions. The effects of dexamethasone injection and dexamethasone liposomes on 4T1 cells were compared by MTT assay. 4T1 BAL B/c tumor-bearing mice model was established and the anti-tumor effect of dexamethasone liposome on 4T1 tumor-bearing mice in vivo was studied. Results When the mass ratio of SPC to DSPE-mPEG2000 was 5:1, the mass ratio of SPC to dexamethasone was 50:3, and the ultrasonic time was 20 min, dexamethasone liposome had the smallest particle size and the narrowest particle size distribution, stable at room temperature for 15 d and stable in physiological medium. MTT data showed that both dexamethasone injection and dexamethasone liposome had a weak inhibitory effect on the growth of 4T1 cells, but the inhibition rate of dexamethasone liposome was 78.9% at 5 mg/kg dosage in vivo, significantly higher than that of dexamethasone injection (33.4%, P < 0.05) and Paclitaxel injection at 8 mg/kg (55%, P < 0.05). Conclusion Dexamethasone liposome can exist stably in physiological medium and can be administered orally and intravenously. Dexamethasone liposome have a strong inhibitory effect on the tumor growth of 4T1 tumor-bearing mice, but the inhibitory effect on 4T1 cells is not strong in vitro. It is speculated that dexamethasone liposome inhibit the growth of tumors by regulating the microenvironment of tumors rather than killing them directly.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金–广东联合基金资助项目(U1401223)