聚乙二醇包裹表阿霉素脂质体的制备及评价

Preparation and evaluation of a liposome of PEG and epirubicin

目的制备聚乙二醇(polyethylene glycol,PEG)包裹表阿霉素脂质体,对其药剂学性质和活性进行评价。方法采用乳化溶剂挥发法制备聚乙二醇包裹表阿霉素的脂质体,用扫描电镜和透射电镜观察其形态,用激光纳米粒度仪测定粒径分布及Zeta电位、并对包封率、稳定性及体外释药特性进行研究,采用MMT法和S180小鼠模型评价体内外抗肿瘤活性。结果聚乙二醇包裹表阿霉素的脂质体的粒径为(231.4±2.0)nm,动电位为(-25.62±0.68)m V,包封率为(53.14±4.85)%,各项稳定性均有明显提高,体外释放缓慢,小鼠剂量可增加到6μmol/kg,给药间隔可延长至72 h,并显示比表阿霉素好的抗肿瘤活性。结论本实验获得了较理想的聚乙二醇包裹表阿霉素脂质体,体外释药符合长效制剂特征,血浆中稳定,具有p H敏感性,可改善表阿霉素用药安全性,延长药物作用时间。

Objective To prepare a novel lipsome of polyethylene glycol packaged with epirubicin （ EPI ） liposomes, to explore the properties of the liposome and evaluate its antitumor activities. Methods Emulsion solvent evaporation method was used to prepare the liposome. The morphology of the liposome was observed by transmission electron microscope （ TEM ） and scanning electron microscope （ SEM） . The characteristics such as particle size, zeta potential, drug entrapment rate, stability and releasing property in vitro were studied. The anti-proliferation activities of EPI liposome and EPI against cancer cells were evaluated by MTT assay. The antitumor activity in vivo was assayed on S180 mouse model. Results The average particle size and the zeta potential of the liposome were （231. 4±2. 0） nm and （-20~30） mV, respectively, and the average entrapment efficiency was （53. 14±4. 85）%. This novel liposome improved the stability, slowed the releasing rate, enhanced the activity, increased the tolerance and extended dosing interval. Conclusion PEG and EPI formed a novel liposome capable of long-acting, plasma-stabile, pH-dependent release, and highly inhibitory effect against tumor growth.