纳米尿激酶的性状研究

Characterization of urokinase chitosan nanoparticles

背景:尿激酶半衰期短,需持续大量给药,并发症也不小,故有必要研制具有缓释作用的溶栓药物。目的:了解包载尿激酶的水溶性壳聚糖纳米粒子的性状。方法:将壳聚糖和三聚磷酸钠以离子凝集法制备尿激酶纳米粒子后,用透射电镜观察其形态,采用粒径仪测纳米粒子粒径,酶标仪比色法测粒子包封率,纳米粒子冻干法测其载药量,并检测体内外纳米粒子缓释特性。结果与结论:当壳聚糖、三聚磷酸钠、尿激酶的质量比为7∶1∶1时,不仅溶液稳定,形成的纳米粒子粒径小,而且包封率和载药量均合适。制备出包封率最高达94.8%的尿激酶纳米粒子,载药量为14.5%,此时平均粒径236nm,透射电镜观察示粒子形态较规则,呈球形;粒子具有较好的缓释性能;表明将尿激酶包被于纳米粒子中,避免了消化酶的直接作用,延长了半衰期,不仅在体内能保持较长时间的活性,而且具有明显的缓释效果。

BACKGROUND： Because urokinase has a short half-life, and has a sustained large dose, resulting in innegligible complications, it is necessary to develop slow-release thrombolytic drugs. OBJECTIVE： To study the characterization of urokinase chitosan nanoparticles. METHODS： The nanoparticles were prepared via the self-assembly of chitosan and sodium tripolyphosphate. The morphololy was observed by transmission electron microscopy （TEM）. Particle size was measured with particle size instrument. The encapsulation efficiency was tested by ELISA Reader. Drug loading efficiency was measured by the way of weighing lyophilized powder. Release characteristics of the nanoparticles were investigated both in vitro and in vivo. RESULTS AND CONCLUSION： When the mass ratio of chitosan, sodium tripolyphosphate, and urokinas was 7：1：1, the solution was stable, the nanoparticle size was small, and drug encapsulation efficiency and loading efficiency were appropriate. When the highest encapsulation efficiency was 94.8%, the drug loading efficiency was 14.5% and mean diameter was 236 nm. TEM displayed that the morphology of nanoparticles was spherical and regular. The nanoparticles had better sustained-release properties, avoided the direct effect of digestive enzymes, and prolonged the half-life of urokinase to maintain a long-term activity in vivo.