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目的:优化阿霉素脂质体处方和制备工艺,利用节拍式低剂量给药化疗方式探讨阿霉素脂质体对HO-8910人卵巢癌细胞的体外杀伤作用.方法:采用硫酸铵梯度法制备脂质体,正交设计优选制备处方;葡聚糖凝胶柱层析法分离含药脂质体与游离药物并测定包封率;考察其体外释放度.以常规给药24h和节拍式低剂量给药144h的形式分别考察阿霉素脂质体、阿霉素体外细胞的毒性作用.结果:所得优化处方为:磷脂与胆固醇的质量比为3∶1,硫酸铵浓度为155mmol/L,药物与磷脂的质量比为1∶10,孵育温度为60℃.以优化处方制得的脂质体平均包封率达92.86%;脂质体具有一定的缓释作用.脂质体的细胞毒性实验结果显示,游离阿霉素与阿霉素脂质体IC50值24h分别为0.62μg/mL和0.46μg/mL,144h分别为0.06μg/mL和0.01μg/mL.结论:优化得到的阿霉素脂质体处方工艺简便,包封率高;无论是游离的阿霉素或是阿霉素脂质体,运用节拍式低剂量给药的方式在H0-8910细胞中抑制率都明显优于MTD化疗方式给药,其中脂质体药物节拍式低剂量给药方式对H0-8910细胞的抑制率明显优于游离药物.
OBJECTIVE: To optimize the formulation and preparation of doxorubicin liposomes and to study the in vitro killing effect of doxorubicin liposomes on HO-8910 human ovarian cancer cells by using low-dose metronomic chemotherapy.Methods: Ammonium sulfate gradient method Preparation of liposomes, the orthogonal design of the preferred preparation of prescriptions; Sephadex column chromatography separation of drug-containing liposomes and free drug and determination of entrapment efficiency; Investigation of its in vitro release.Using routine and 24h 144h hypoxia and doxorubicin in vitro.Results: The optimized formulation was as follows: the mass ratio of phospholipid to cholesterol was 3:1, the concentration of ammonium sulfate was 155mmol / L , The mass ratio of drug to phospholipid was 1:10 and the incubation temperature was 60 ° C. The average entrapment efficiency of liposomes was 92.86% with optimized formulation.The liposomes had some sustained release.Liposomes cells Toxicity test results showed that IC50 values of free doxorubicin and doxorubicin liposomes were 0.62μg / mL and 0.46μg / mL for 24 h, respectively, and 0.06 μg / mL and 0.01 μg / mL for 144 h respectively.Conclusion: Docetaxel liposomes process is simple, high entrapment efficiency; either free or doxorubicin Liposomes, the use of low-dose beat mode of administration in H0-8910 cells were significantly better than the inhibition rate of MTD chemotherapy, in which liposomal drug beats low-dose administration of H0-8910 cells Inhibition rate was significantly better than free drugs.