透明质酸磷脂酰衍生物修饰姜黄素脂质体的制备及细胞毒性

Preparation and Cytotoxicity of Hyaluronic Acid Phosphatidyl Derivative Modified Curcumin Liposomes

采用逆相蒸发法制备了姜黄素脂质体。由于透明质酸脂溶性较差,先将其制成磷脂酰衍生物(透明质酸-磷脂酰乙醇胺,HA-DOPE),再用以修饰载药脂质体。所得脂质体的平均包封率为89%,该衍生物与脂质体的结合率为72%。脂质体于4℃保存30 d包封率无明显改变,但结合率有轻微下降。细胞毒性试验显示,游离姜黄素、姜黄素脂质体及修饰后脂质体对高表达CD44受体的人肺腺癌A549细胞的IC50值分别为0.054、0.032和0.021 mol/ml,未修饰和修饰后的姜黄素脂质体对低表达CD44受体的人肝癌HepG2细胞作用相当。

The curcumin liposomes were prepared by the reverse-phase evaporation method. Hyaluronic acid was first converted into its phosphatidyl derivative （HA-DOPE）, which was used to modify the prepared liposomes. The average entrapment efficiency was 89 % and binding rate of HA-DOPE to liposomes was 72 %. After storing at 4 ℃ for 30 d, the entrapment efficiency of product did not change significantly, but the binding rate decreased slightly. The IC50 values were found to be 0.054, 0.032 and 0.021 μmol/ml for free curcumin, curcumin liposomes and modified curcumin liposomes, respectively after incubation with A549 cells overexpressing CD44 receptor. The unmodified and modified curcumin liposomes had similar cytotoxicity effect on HepG2 cells underexpressing CD44 receptor.