盐酸米托蒽醌聚乙二醇化脂质体的制备及对A549细胞体外抗肿瘤作用的研究

Preparation of mitoxantrone hydrochloride PEGylated liposomes and its in vitro antitumor effects on tumor cell A549

目的研究盐酸米托蒽醌聚乙二醇化脂质体(DHAD-PEG-L)的制备及其抗肿瘤细胞增殖作用,比较DHAD-PEG-L与常规盐酸米托蒽醌(DHAD)制剂的抗肿瘤活性差异。方法以主动载药法制备获得DHAD-PEG-L;以人非小细胞肺癌A549细胞为模型,采用MTT法考察DHAD-PEG-L和DHAD对肿瘤细胞的抑制效果,测定制剂作用肿瘤细胞48 h后的IC_(50)值;以方差分析法比较DHAD-PEG-L与DHAD抗肿瘤活性的统计学差异。结果 DHAD-PEG-L和DHAD对A549细胞的IC_(50)分别是(1.561±0.09)mg·L^(-1)和(0.862±0.02)mg·L^(-1);药物经聚乙二醇(PEG)脂质体包封后,与常规制剂相比,高浓度时肿瘤抑制作用略有下降,低浓度时抑制作用增强。结论 PEG化技术可运用于脂质体,对DHAD进行减毒增效改造,预期可降低药物不良反应。

Objective To study the preparation of mitoxantrone hydrochloride PEGylated Liposomes(DHAD-PEG-L) and its in vitro antitumor effects. Compared the differences of in vitro antitumor effects of DHAD-PEG-L and conventional preparations(DHAD). Methods DHAD-PEG-L was prepared by ammonium sulfateion gradient technique. Observed the antitumor effects of DHAD-PEG-L and DHAD with the model of non-small cell lung cancer cell A549 by MTT method. IC_(50) value was determined after interaction with cancer cell for 48 h. Compared the antitumor difference of those two preparations by ANOVA statistical method. Results The IC_(50) value in A549 were(1.561±0.09) mg · L^(-1) and(0. 862 ±0. 02) mg ·L^(-1). After encapsulated in liposomes,the drug antitumor effects decreased when used in high concentration, but increased while used in low concentration. Conclusion Preliminary results suggest that PEGylated liposomes could be chosen for the preparation modification of mitoxantrone hydrochloride to reduce ADR.