摘要
目的 研究两种方法制备的葡聚糖 表柔比星偶合物的稳定性及体外细胞毒活性。方法 采用高碘酸钠氧化法制备聚醛基葡聚糖 表柔比星偶合物 (PAD EPR) ,将葡聚糖羧甲基化后制备腙健连接的羧甲基葡聚糖 表柔比星偶合物 (CMD EPR)。结果 PAD EPR的载药量为 1∶4,CMD EPR的载药量为 1∶10 ;二者在中性条件下均比较稳定 ,4℃贮存 70d ,药物偶合率都在90 %以上。偶合物的体外细胞毒性比游离药物有所下降 ,游离药物对正常细胞的毒性高于对肿瘤细胞的毒性 ,CMD EPR对肿瘤细胞的毒性高于对正常细胞的毒性 ,PAD EPR对两种细胞的毒性没有差异。结论 CMD EPR优于PAD
OBJECTIVE To study the stability and in vitro cytotoxicity of two kinds of dextran epirubicin conjugates.METHODS Polyaldehyde dextran epirubicin (PAD EPR) was made by sodium periodate oxidation.Carboxy methyldextran epirubicin(CMD EPR) was made by chloroacetic acid carboxymethylation followed by conjugating in hydrazone bond.RESULTS The ratio of carrier/drug of PAD EPR was 1∶4,while that of CMD EPR was 1∶10.Both of the conjugates were stable,with the conjugated drugs more than 90% after 70 days storgae at 4℃.The in vitro cytotoxicity of the conjugates was lower than that of the free drug.CMD EPR was more effective against tumor cells with less cytotoxicity to non tumor cells than the free EPR.There was no difference for PAD EPR in inhibiting non tumor or tumor cells.CONCLUSION CDM EPR is prior to RAD EPR in the view of the cytotoxieity to tumor cells.
出处
《中国药学杂志》
EI
CAS
CSCD
北大核心
2000年第7期455-457,共3页
Chinese Pharmaceutical Journal
基金
总后医药科技"八五"攻关项目! (91A0 0 3-0 0 37)
关键词
葡聚糖表柔比星
偶合物
稳定性
细胞毒性
polyaldehyde dextran
carboxymethyldextran
epirubicin
conjugates
stability
cytotoxicity
