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目的考察采用不同工艺制备的酒石酸长春瑞滨脂质体注射液(vinorelbine tartrate liposome injection,VLI)的药剂学性质及抗肿瘤效果。方法采用pH梯度法、硫酸铵梯度法和蔗糖八硫酸酯三乙胺(SOS-TEA)梯度法,结合PEG外导入法,制备酒石酸长春瑞滨脂质体注射液-1、酒石酸长春瑞滨脂质体注射液-2、酒石酸长春瑞滨脂质体注射液-3;观察3种脂质体形态,并测定3种脂质体的粒径及Zeta电位、包封率、体外释放、稳定性等药剂学特性;以酒石酸长春瑞滨注射液(vinorelbine tartrate injection,VI)为对照,采用人结肠癌HT-29移植肿瘤模型,比较3种脂质体在裸鼠体内抑制肿瘤效果和一般毒性。结果 3种脂质体药物包封率均大于93%,平均粒径80~100 nm,Zeta电位约为-15 mV,2~8℃条件下放置6个月各样品的主要质量指标均未发生明显变化;3种脂质体均缓慢释放,以酒石酸长春瑞滨脂质体注射液-3药物释放速度最慢。冷冻透射电镜观察形态结果表明,酒石酸长春瑞滨脂质体注射液-1中药物以溶液形态存在于脂质体内部,而酒石酸长春瑞滨脂质体注射液-2和-3内部可观察到胶体状和针状结晶。药效学研究结果表明,采用酒石酸长春瑞滨脂质体注射液-3疗效优于酒石酸长春瑞滨脂质体注射液-2和酒石酸长春瑞滨脂质体注射液-1,而酒石酸长春瑞滨脂质体注射液-1和酒石酸长春瑞滨脂质体注射液-2疗效均略优于酒石酸长春瑞滨注射液。结论酒石酸长春瑞滨脂质体注射液-3在抗肿瘤细胞生长方面与酒石酸长春瑞滨注射液相比具有显著优势,毒性低。
Objective To investigate the pharmacological properties and antitumor effects of vinorelbine tartrate liposome injection (VLI) prepared by different techniques. Methods The pH gradient method, ammonium sulfate gradient method and sucrose octasulfate triethylamine (SOS-TEA) gradient method combined with PEG external introduction method were used to prepare vinorelbine tartrate injection-1, vinorelbine tartrate Plastid injection-2 and vinorelbine tartrate injection-3. The morphology of three kinds of liposomes was observed. The three kinds of liposomes were determined by their particle size, zeta potential, encapsulation efficiency, in vitro release and stability And other pharmacological properties. The tumor model was transplanted with human colon cancer HT-29 using vinorelbine tartrate injection (VI) as a control. The antitumor effects and general toxicity of the three liposomes in nude mice were compared. Results The entrapment efficiencies of the three liposomes were all above 93% with an average diameter of 80-100 nm and a zeta potential of -15 mV. The main quality indexes of all the samples did not appear after 6 months at 2-8 ℃ Obviously changed. All three liposomes released slowly, and the release rate of drug was the slowest with the injection of vinorelbine tartrate injection-3. The results of cryo-TEM observation showed that the drug of vinorelbine-tartrate injection-1 existed in the form of solution in the liposomes, whereas the vinorelbine-tartrate injection of 2 and 3 could be observed in the liposomes Colloidal and acicular crystals. Pharmacodynamics results show that the use of vinorelbine tartrate injection-3 efficacy is better than vinorelbine tartrate injection-2 and vinorelbine tartrate liposome injection -1, and vinorelbine tartrate Binoposome injection -1 and vinorelbine tartrate injection-2 efficacy are slightly better than Vinorelbine tartrate injection. Conclusions Vinorelbine tartrate injection-3 has significant advantages over vinorelbine tartrate injection in anti-tumor cell growth with low toxicity.