脂质-磷酸钙核/壳纳米粒作为抗肿瘤药物载体的初步研究  

Preliminary study of lipid bilayer-coated calcium phosphate nanoparticles as a drug carrier for antitumor drug

作　　者：缪云秋 何淑芳[2] 梁金英[2] 柯琴[2] 张馨欣[2] 王瑞[1] 甘勇[2] 

机构地区：[1]上海中医药大学中药学院,上海201203 [2]中国科学院上海药物研究所,上海201203

出　　处：《药学学报》2017年第6期977-984,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81571796)

摘　　要：本文拟构建一种新型的脂质-磷酸钙核/壳纳米粒(lipid bilayer-coated calcium phosphate nanoparticles,LCAPNs)可在胞内溶解实现迅速释药,以提高抗肿瘤药物对肿瘤细胞的杀伤活性。采用薄膜分散法合成制备了包载紫杉醇(paclitaxel,PTX)的脂质-磷酸钙核/壳纳米粒(lipid bilayer-coated calcium phosphate nanoparticles loaded with PTX,PTX-LCAPNs),并对其进行形态、粒度和体外释放行为的表征。同时,以人肝癌细胞Huh-7为细胞模型,考察载体的细胞摄取、胞内溶解特性、药物胞内蓄积量和抗肿瘤活性。研究结果表明:LCAPNs在透射电镜下呈球形,平均粒径为124.73±6.41 nm。载体在体外模拟正常生理p H条件下PTX泄漏量低,而在胞内酸性p H环境中快速释药。另外,LCAPNs可有效提高Huh-7细胞对药物的摄取量,并且在胞内溶解以快速释药。PTXLCAPNs显著增加PTX对肿瘤细胞的杀伤力,将包载紫杉醇的磷酸钙纳米粒(calcium phosphate nanoparticles loaded with PTX,PTX-CAPNs)的胞内药物浓度提高了1.7倍,半数抑制浓度(IC50)降低了约5倍,抗肿瘤效果显著增强。This study aims to prepare lipid bilayer-coated calcium phosphate core-shell nanoparticles （LCAPNs）, which can dissolve in an acidic environment to improve the tumor cell toxicity of antitumor drug. Paclitaxel （PTX） loaded lipid coated calcium phosphate nanoparticles （PTX-LCAPNs） were prepared by thin-film dispersion method. The morphology, particle size and in vitro release behavior were characterized. Meanwhile, the intracellular uptake, intracellular dissolution, cell toxicity of PTX-LCAPNs and intracellular accumulation of PTX were evaluated in human HCC cell line （Huh-7）. The results suggested that the mean diameter of the spherical LCAPNs was 124.73 ~6.41 nm. The PTX-LCAPNs demonstrated little drug leakage in simulated normal physiological conditions, while a rapid release was observed in simulated intracellular condition in vitro. Moreover, the PTX-LCAPNs achieved 1.7 fold improvement in the intracellular PTX concentration leading to 5-fold reduction in half maximal inhibitory concentration （IC 50） values of PTX compared with calcium phosphate nanoparticles loaded with PTX （PTX-CAPNs）, demonstrating a stronger cancer cell lethality.

关 键 词：磷酸钙 纳米粒 紫杉醇 释药 抗肿瘤药物 

分 类 号：R943[医药卫生—药剂学]