5-FU-PLA微球的肺癌杀伤效应研究

Studies on release characteristics and cytotoxicity of 5-fluorouracil loaded polylactide microspheres on lung cancer cell lines

目的 研究生物可降解抗癌药 5 FU PLA微球的释药特点 ,鉴定其体外杀伤肿瘤细胞的活性。方法 采用恒温振荡透析法和一阶导数紫外分光光度法测定 5 FU PLA微球的药物释放特性 ;MTT比色法测定不同时相 5 FU PLA微球对人和小鼠肺癌、胃癌、肝癌等细胞株的杀伤活性。结果 5 FU PLA微球的半数释放期 (t 1/ 2 )为 10 .4天 ,释放过程未表现出爆破效应 ( 2 4小时释放 19.4% )。 5 FU PLA微球对肺癌等细胞株有较强杀伤活性 ,其中肺癌和胃癌较肝癌更为敏感 ;5 FU PLA微球的肿瘤杀伤活性与作用时间和释药量呈正相关关系。结论 5 FU PLA微球的抗癌药物分布均匀 ,具有良好的缓释功能 ,微球制备和释放过程对 5 FU的药效无影响。 5 FU PLA微球能在较长时间内维持有效的杀瘤活性。本研究为 5 FU PLA微球用于肺癌等肿瘤的介入治疗提供了实验依据。

Objective To investigate the release characteristics and cytotoxicity of 5 fluorouracil loaded polylactide microspheres on lung cancer cell lines. Methods The release characteristic of 5 FU PLA microspheres was detected by constant temperature vibration dialysis assay. The antitumor activities of 5 FU PLA microspheres against human and mouse lung, gastric and hepatocellular carcinoma cell lines were detected by MTT colorimetric assay. Results 5 FU PLA microspheres had a good function of extended release, its t 1/2 was 10.4 days, and the release process had no blow up effect. The lung and gastric cancer cell lines were more sensitive than hepatocellular cancer cell line to 5 FU PLA microspheres. The antitumor activity significantly correlated with the time of drug action and the dose of 5 FU released from the microspheres. Conclusion 5 FU is well distributed in 5 FU PLA microspheres. Its preparing and releasing processes have no influence on the effect of 5 FU. It can keep the antitumor activities for a relatively long time. The current study provides an experimental basis for interventional therapy of tumors.