摘要
目的 制备血栓靶向的尿激酶脂质体 ,并在大鼠颈总动脉血栓模型上考察其溶栓情况。方法 通过液相合成法合成出靶向于血栓的特异性配体H Arg Gly Asp Ser OH (RGDS) ,并将其与monocarboxylpoly (ethyleneglycol)35 0 0distearoylphosphatidylethalnolamine (DSPE PEG350 0 COOH)偶联后插入到脂质体双层膜中得到血栓靶向尿激酶脂质体 ;通过制备方法的改进 ,以氢化豆磷脂在室温下制备尿激酶脂质体 ;在大鼠颈总动脉血栓模型上 ,考察了血栓靶向脂质体的体内溶栓效果。结果 所得的尿激酶脂质体包封率高、粒径小 ,稳定性好 ;与空白对照组的栓重相比 ,在相同剂量 (6 0kU·kg- 1 ,小剂量 )下 ,游离尿激酶组几乎无任何改变 ,尿激酶脂质体组血栓重量稍有减轻但无显著性差异 ,血栓靶向尿激酶脂质体组血栓重量明显减轻 (P <0 0 0 1) ;干重时的情况略有不同。与同剂量的普通脂质体相比 ,血栓靶向尿激酶脂质体溶栓效果显著改善 (湿重时P <0 0 1,干重时P <0 0 5 ) ,表现出明显的靶向溶栓能力。
Aim To prepare thrombus targeted urokinase liposomes and observe its improved thrombolytic efficacy on thrombus model rats. Methods The ligand H Arg Gly Asp Ser OH (RGDS) which has specific affinity to thrombus was synthesized by liquid phase method and anchored on the surface of liposomes by incorporating its conjugate with DSPE PEG 3 500 COOH into liposomal lipid bilayers, thus thrombus targeted liposomes were produced. Urokinase (UK) liposomes were prepared at room temperature through method modification using hydrogenated soy phosphatidylcholine (HSPC); the in vivo thrombolysis of the obtained thrombus targeted UK liposomes and its comparison with TBS (Tris HCl buffered solution) control, free UK and UK liposomes were assessed on common carotid artery model rats. Results The obtained liposomes were characteristic of high UK entrapment efficiency, small mean diameter and good storage stability. At the same dose ( 60 000 U·kg -1 ), compared to the wet thrombi weights of TBS control group, those of free UK group and UK liposome group showed no statistical difference, while those of targeted UK liposomes group were significantly decreased ( P <0 001); when evaluated in term of dry thrombi weights the result was slightly different. Compared to UK liposomes of the same dose, the targeted UK liposomes showed significantly improved thrombolytic efficacy ( P <0 01 in wet weights decrease and P <0 05 in dry weights decrease respectively). Conclusion The targeted UK liposomes displayed good targeted thrombolytic effect.
出处
《药学学报》
CAS
CSCD
北大核心
2003年第3期231-235,共5页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目 (3 0 171114)
关键词
血栓靶向
RGDS
尿激酶
脂质体
颈总动脉血栓模型
thrombus targeted
RGDS
urokinase
liposomes
common carotid artery thrombus model
