摘要
将鱼精蛋白与琥珀酰化去氧胆酸在交联剂作用下偶联,制备3种不同偶联度的鱼精蛋白-去氧胆酸偶联物（DP1~DP3）。选择偶联度为32%的DP3,通过静电作用与肝素钠形成稳定的纳米复合物。考察了DP3与肝素钠不同质量比下所得纳米复合物的粒径、ζ电位和载药能力。结果表明,DP3与肝素钠质量比为1.5∶1时,DP3包载肝素钠的能力趋于饱和。此时得到的纳米复合物粒径为（136.0±2.5）nm,多分散系数为0.164±0.005,ζ电位为（＋32.6±0.1）m V。与游离肝素钠相比,该纳米复合物能有效提高肝素钠向人肺腺癌A549细胞内的传递效率,并对A549肿瘤细胞呈现较高的生长抑制作用,而DP3未见明显的细胞毒性。
The protamine-deoxycholic acid conjugates with different conjugation degrees （DP1 - DP3） were synthesized through the reaction between protamine and N-hydroxysuccinimide ester of deoxycholic acid. The DP3 with conjugation degree of 32% was used to prepare the stable nanocomplexes loaded with heparin sodium via electrostatic interaction. The particle size, ζ potential and drug loading capacity of the nanocomplexes with different feed weight ratios of DP3 to heparin sodium were investigated. The results showed that when the ratio of DP3 to heparin sodium was 1.5 ： 1, the loading capacity was nearly saturated. Under this preparation condition, the particle size, polydispersity index and ζpotential of the nanocomplexes were （136.0±2.5） nm, 0.164±0.005 and （＋32.6±0.1） mV, respectively. Compared with the free heparin sodium, the above complexes could effectively induce intracellular delivery of heparin sodium into human lung adenocarcinoma A549 cells. The cytotoxicity assay in vitro showed that the nanocomplexes had a strong growth inhibition effect on A549 cells while DP3 had no marked cytotoxicity.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2015年第11期1192-1196,1263,共6页
Chinese Journal of Pharmaceuticals
基金
国家自然科学基金青年基金(21306066)
江苏省自然科学基金青年基金(BK2012557)
关键词
鱼精蛋白
去氧胆酸
肝素
纳米复合物
制备
抗肿瘤活性
protamine
deoxycholic acid
heparin
nanocomplex
preparation
anti-tumor activity
