羟基喜树碱-磷脂复合物的制备、表征及细胞毒性评价

Preparation,characterization and in vitro cytotoxicity evaluation of hydroxycamptothecin-phospholipid complex

目的制备羟基喜树碱-磷脂复合物(HCPT-PC),对其理化性质进行表征,并考察其细胞毒性。方法采用马尔文粒径电位测定仪、扫描电镜、透射电镜对粒径和形态进行表征;采用X线粉末衍射、红外光谱对复合机制进行考察;同时考察其溶解度和抗肿瘤活性。结果 HCPT-PC粒径为(145.08±18.37)nm;扫描电镜和透射电镜下呈均匀分布的球形;粉末衍射结果显示,HCPT-PC中HCPT从结晶态转变为无定形状态;红外光谱显示HCPT与PC的极性端存在弱相互作用;HCPT-PC在水、PBS、乙醇、正辛醇中的溶解度分别提高约21.91、20.36、1.42和6.32倍;与Hep G2、SMMC-7721和H22细胞作用48和72 h后,HCPT-PC的IC50值较HCPT分别提高3.57、11.14、2.79、37.26、21.23和24.49倍。结论 HCPT通过与PC的极性端形成弱相互作用复合成无定形状态的HCPT-PC,其溶解度和抗肝癌活性较HCPT显著提高。

Objective To prepare hydroxycamptothecin-phospholipid complex（HCPT-PC）,characterize its physicochemi-cal properties,and evaluate the cytotoxicity. Methods The particle size and morphology of HCPT-PC were characterized by malvern particle size potentiometer,scanning electron microscopy（TEM）and transmission electron microscopy（TEM）. Its composite mecha-nism was investigated by X-ray powder diffraction and infrared spectroscopy. The solubility and antitumor activity were also investigat-ed. Results The particle size of HCPT-PC was（145.08＆#177;18.37）nm. Scanning electron microscopy and transmission electron micros-copy revealed that HCPT-PC was uniformly distributed with a spherical shape. X-ray powder diffraction indicated that HCPT changed from crystalline to amorphous state in HCPT-PC. Fourier transform infrared spectroscopy showed that there was a weak interaction be-tween HCPT and PC. The solubility of HCPT-PC in water,PBS,ethanol and n-octanol was about 21.91,20.36,1.42 and 6.32 times than that of HCPT,respectively. After treated with HepG2,SMMC-7721 and H22 cells for 48 and 72 hours,IC50 of HCPT-PC was higher than that of HCPT by 3.57,11.14,2.79,37.26,21.23 and 24.49 times,respectively. Conclusion HCPT is compounded into an amorphous-state HCPT-PC by a weak interaction with the polar end of PC. Its solubility and anti-hepatocarcinoma activity are signif-icantly higher than HCPT.