葡萄糖修饰的不同PEG作为桥联脂质体的体外特性研究

目的 制备用葡萄糖修饰以不同聚合度的PEG作为桥联的脂质体,并考察其体外特性.方法 以香豆素6为荧光探针,用薄膜分散法制备葡萄糖修饰的以PFG400、PEG800、PEG2000作为桥联的载香豆素6脂质体,用激发光散射粒度测定仪测定其粒径;用凝胶柱层析法测定其包封率;在含10%胎牛血清的磷酸盐缓冲液（PBS）中考察其稳定性;以大鼠脑毛细血管内皮细胞（BCECs）为受试细胞,对载香豆素6的不同类型脂质体进行细胞摄取的定量分析.结果 葡萄糖修饰的以PEG400、PEG800、PEG2000作为桥联的脂质体的粒径分别为（81.5±6.3）、（100.0±5.0）、（104.9±8.7）nm,多分散系数（PDI）分别为（0.252±0.016）、（0.265±0.032）、（0.289±0.013）;其包封率均〉80%;在含10%胎牛血清的PBS中具有较好的稳定性;葡萄糖修饰的以PEG800、PEG2000作为桥联的脂质体在BCECs中的细胞摄取率均高于普通脂质体.结论 本研究成功制备了葡萄糖修饰的以PEG400、PEG800、PEG2000作为桥联的脂质体,研究初步显示以PEG800、PEG2000为桥联的脂质体有一定脑靶向潜力.

In vitro characteristics of glucose-modified liposomes using polyethylene glycol with different chain lengths as the linker

Objective To prepare and study the in vitro characteristics of glucose-modified liposomes using polyethylene glycol （PEG） as the linker. Methods Glucose-modified coumarin 6-loaded liposomes using PEG400, PEGS00, and PEG2000 as the linker were prepared by film dispersion method, in which coumarin 6 served as the fluorescent probe. Particle sizes and zeta potentials of liposomes were recorded on Malvern Zetasizer Nano ZS90. The encapsulation efficiency of liposomes was determined by gel column chromatography. The stability of various liposomes was investigated after 24 h incubation in fetal bovine serum （10%）. The uptake of various coumarin 6-loaded liposomes by rat brain capillary endocethelial cells （BCECs） was quantitatively analyzed. Results The average sizes of glucosemodified liposomes using PEG400, PEGS00, and PEG2000 as the linker were （81.5±6.3）, （100. 0±5.0）, and （104. 9±8. 7） nm, with the PDI of （0. 252±0. 016）, （0. 265±0. 032）, and （0. 289±50. 013）, respectively. The en- capsulation efficiency of liposomes was higher than 80%. Glucose-modified coumarin 6-loaded liposomes using PEG400, PEG800, and PEG2000 as the linker were stable after 24 h incubation in fetal bovine serum （10%, v/v）. The uptake efficiency of liposomes using PEG800 and PEG2000 as the linker by BCECs was higher than that of traditional liposomes, and the effect of liposomes using longer PEG as the linker was inhaneed. Conclusion The glucosemodified liposomes using PEG800 and PEG2000 as the linker have the potential of brain targeting.