表面双膦酸盐修饰的丹参素脂质体稳定性及骨靶向性研究

Study on Stability and Bone-targeting of Danshensu-loaded Liposomes Surface-modified with Bisphosphonates

目的:制备骨靶向丹参素脂质体并研究其理化性质。方法:采用逆向蒸发法制备靶向性脂质体。透射电镜观察脂质体的形态,HPLC测定脂质体中丹参素含量,考察骨靶向脂质体在室温下的稳定性,透析法考察脂质体在血浆存在条件下的体外释放度,并采用羟磷灰石晶体吸附试验考察目标物的骨靶向性。结果:表面修饰制备的靶向载药脂质体呈圆球形,室温下为稳定的乳白色混悬液。5天内测得的包封率为31.1%,渗漏率为20.5%。在血浆条件下脂质体有明显的缓释作用,24 h累计释放量为84.6%。表面修饰的脂质体有骨靶向性,羟基磷灰石吸附量随靶向物含量的增加而增加。结论:表面修饰的丹参素脂质体具有骨靶向性,且缓释作用明显。

Objective： To prepare Danshensu liposomes surface-modified with bisphosphonates and investigate the characteristics in vitro. Methods： The liposomes were prepared by a reverse-phase evaporation method and modified with bisphosphonates. The morphology of the liposomes was investigated under a transmission electron microscope. The concentration of Danshensu was determined by HPLC. The stability of the liposomes was investigated and the release characteristics from the liposomes were measured by a dialysis method. Hydroxyapatite-binding assay was performed to observe the bone-targeting of the liposomes. Results ： The morphology of the liposomes was spherical with uniform diameter. The liposoems was stable milky suspension under room temperature. The encapsulation efficiency and percolation rate in 5 days was 31.1% and 20.5% , respectively. The cumulative release of the liposomes in plasma was 84.6% in 24 h, showing notable sustained release property. The surface-modified liposomes showed significant bone-targeting, and the hydroxyapatite-binding was enhanced by the concentration increase of the targeting liposomes. Conclusion： The liposomes surfacemodified with bisphosphonates has strong affinity to bone with sustained release effect.