【摘要】 目的制备紫杉醇脂质体并对其理化性质、毒性及药效学进行初步研究。方法将大豆卵磷脂(soybean Phosphatidyl-choline,SPC)、培化磷脂酰乙醇胺(mPEG2000-DSPE)及紫杉醇以100∶0.5∶5(摩尔比)混合并溶解于氯仿中,采用油水相研磨成乳,然后高压均质的方法制备脂质体。采用低速离心法测定包封率,动态光散射法测定粒度分布,KM鼠进行毒性实验,H22/KM小鼠为模型进行药效实验。结果脂质体平均粒径为(140±10)nm;药脂摩尔比在3%～6%内包封率均大于95%;毒性实验表明,紫杉醇脂质体(Pac-lipo)和紫杉醇游离药(Pac-free)对KM雄性小鼠的最大耐受剂量(MTD)分别为64.8和29.4 mg·kg-1;药效实验表明,紫杉醇脂质体剂量依赖性的抑制鼠肝癌H22肿瘤生长。结论紫杉醇脂质体具有较高包封率,与紫杉醇游离药相比可以显著提高治疗指数。更多还原

【Abstract】 OBJECTIVE To prepare the paclitaxel liposomes and evaluate its physicochemical property,toxicity and pharmacodynamics.METHODS SPC,mPEG2000-DSPE and paclitaxel were dissolved in chloroform in a mole ratio of 100∶0.5∶5.Oil phase and water phase were mixed and skived.The emulsion was homogenized to form liposomes.The mean diameter of liposomes was determined by dynamic light scattering(DLS) techniques.Low-speed centrifugation was employed to determine encapsulation efficiency(EE).The maximum tolerated doses(MTD) was determined in normal KM mice,and antitumor effect was evaluated in H22/KM mice xenograft tumor model.RESULTS The mean diameter of paclitaxel liposomes was(140±10) nm.The EE was over 95 % when the molar ratio of paclitaxel to SPC ranged from 3% to 6%.The MTDs of Pac-lipo and Pac-free in male KM mice were 64.8 and 29.4 mg·kg-1,respectively.Pac-lipo inhibited H22 tumor weight dose-dependently.CONCLUSION Pac-lipo had a high EE,and could increase the therapeutic index significantly,compared with Pac-free.更多还原