摘要
目的:比较顺铂脂质体和顺铂纳米粒细胞转运和抗肿瘤作用的差异,探讨载体种类对药物传递的影响。方法:制备得到粒径、电位、载药量、释放曲线相近的顺铂脂质体和明胶纳米粒,考察二者在A549细胞中的细胞摄取和消除动力学情况,通过内吞抑制剂研究颗粒入胞途径。利用MTT试验评价纳米载体的抗肿瘤活性。结果:两种载体主要通过clathrin介导的内吞途径和大胞饮入胞,顺铂纳米粒摄取水平显著高于脂质体。而后者的胞内滞留能力远高于前者,平均滞留时间(MRT)为纳米粒组的3倍,曲线下面积(AUC)约为纳米粒2倍。MTT结果表明,顺铂脂质体的抗肿瘤活性远高于明胶纳米粒,IC50分别为(2.94±0.21、20.70±1.05)μg/m l。结论:制剂参数相近的两种纳米粒在细胞摄取、消除的药物传递过程中有较大的区别,引起体外抗肿瘤活性的差异。与纳米粒相比,脂质体是更适合顺铂发挥疗效的纳米载体。
Objective:To compare the differences in antitumor activity between cisplatin(CDDP)-loaded liposomes and nanoparticles in vitro.Methods:CDDP-gelatin nanoparticles(GPs-Pt) and CDDP-liposomes with similar size,zeta potential,drug loading efficiency and in vitro release property were prepared.The uptake in A549 cells and elimination kinetics were evaluated and antitumor activity was determined by MTT test.The internalization pathways of nanocarriers were studied with inhibitors.Results:Internalization of two nanocarriers was clathrin and actin dependent.Pt accumulation delivered by GPs-Pt was significantly higher than that of liposomes.However,the results of kinetic analysis showed that liposomes had longer cellular retention,and the MRT and AUC were 3 times and twice of GPs-Pt,respectively.The IC50 of liposomes was significantly lower than GPs-Pt.The values were 2.94±0.21 and 20.70±1.05 μg/ml,respectively.Conclusions:Nanocarriers with similar pharmaceutical parameters can induce differences in cellular internalization and elimination,which influence the antitumor activity eventually.Compared with gelatin nanoparticle,liposome is preferable for cispaltin delivery.
出处
《浙江大学学报(医学版)》
CAS
CSCD
北大核心
2011年第4期408-413,共6页
Journal of Zhejiang University(Medical Sciences)
基金
国家自然科学基金(30873176)
浙江大学城市学院教师基金(581646)
关键词
顺铂
治疗应用
肿瘤
药物疗法
脂质体
明胶
纳米粒
抗肿瘤
Cisplatin/ther use
Neoplasms/drug ther
Liposomes
Gelatin nanoparticles
Antitumor activity
Comparative study