N,N-二羟乙基甘氨酸-氢氧化钠缓冲液制备的过氧化氢酶复合纳米脂质体的特性分析及过氧化氢酶的药效学初步研究

目的:研究过氧化氢酶(catalase, CA)/尿酸酶(uricase, UA)复合纳米脂质体(catalase and uricase nanoliposome, CULP)中过氧化氢酶在大鼠体内的药效学。方法:采用逆向蒸发法制备了CULP,用激光粒度仪测定平均粒径。测定CULP及CA的最适温度和最适pH值。大鼠静脉注射过氧化氢建立高过氧化氢大鼠模型,建模后分别静脉注射CULP和CA,测定不同时间点大鼠血清中过氧化氢的浓度。结果:CULP的平均粒径为1 000 nm。CULP和CA最适温度均为40℃,最适pH值分别为为8.0和7.0。在同一温度和pH条件下,CULP中CA的活性高于游离CA;且CULP在大鼠体内降低过氧化氢浓度的能力高于游离CA。结论:CULP在大鼠体内降低过氧化氢水平的能力优于游离CA,为过氧化氢酶的临床应用提供实验依据。

Preliminary study on property and pharmacodynamics of nanoliposomes containing catalase and uricase prepared in bicine-sodium hydroxide buffer

OBJECTIVE To investigate pharmacodynamics of catalase (CA) in catalase-uricase nanoliposomes (CULP) in rats.METHODS CULP were prepared by reverse-phase evaporation method, and optimal temperature and pH value were detected. Mean particle size was examined by a laser sizer. Rats were intravenously injected hydrogen peroxide to construct high hydrogen peroxide model. Serum hydrogen peroxide concentrations at different times were assayed after intravenous injection of CULP and CA in rats.RESULTS Average diameter was 1 000 nm. Both optimal temperatures for CULP and CA were 40℃, while optimal pH values were 8.0 and 7.0, respectively. Activity of CULP was higher than that of CA at the same temperature and pH value. CULP was more effective in decreasing hydrogen peroxide in rats.CONCLUSION CULP is significantly superior in decreasing high hydrogen peroxide level in rats to CA, which provides an experimental basis for clinical application of CA.