产朊假丝酵母尿酸酶脂质纳米粒的制备及其药效学特性分析

目的制备产朊假丝酵母尿酸酶(uricase,URI)脂质纳米粒,并分析其药效学特性。方法采用旋转蒸发法制备3批URI脂质纳米粒(lipid nanoparticles containing uricase from Candida utilis,LNURI),检测其包封率、URI活性、酶的最适作用温度和最适作用pH值。采用次黄嘌呤和氧嗪酸钾建立高尿酸大鼠模型,分别于建模后1 h经尾静脉注射LNURI和游离URI,建模后3、5、7、8、12 h,测定大鼠血清中尿酸水平。结果制备的3批LNURI的平均包封率为(64.27±2.26)%;LNURI的最适作用温度为40℃,最适作用pH值为8.0,在同样的作用温度和pH值条件下,LNURI的活性明显高于游离URI;LNURI降低高尿酸模型大鼠血清中尿酸水平的效果较URI更显著。结论成功制备了产朊假丝酵母尿酸酶脂质纳米粒,其可降低高尿酸模型大鼠血清中尿酸水平。

Preparation and pharmacodynamics of lipid nanoparticles containing uricase from Candida utilis

Objective To prepare the lipid nanoparticles containing uricase(URI) from Candida utilis(LNURI) and analyze their pharmacodynamics.Methods Three batches of LNURI were prepared by rotary evaporation method,and determined for entrapment efficiency,URI activity as well as optimal temperature and pH value.Rat model of hyperuricemia was established with hypoxanthine and potassium oxonate.The model rats were injected i.v.with LNURI and free URI 1 h,and determined for serum uric acid level 3,5,7,8 and 12 h after establishment.Results The mean entrapment efficiency of three batches of LNURI was(64.27 ± 2.26)%.The optimal temperature and pH value of LNURI were 40℃ and 8.0 respectively.The activity of LNURI was significantly higher than those of free URI at the same temperature and pH value.However,as compared with free URI,LNURI was more effective in decreasing the serum uric acid level of rats with hyperuricemia.Conclusion LNURI were successfully prepared,which decreased the serum uric acid level in rats with hyperuricemia.