透明质酸修饰的尿酸酶多囊脂质体的体外特性及药效学过程

目的 研究透明质酸修饰的尿酸酶(UC)多囊脂质体(uricase in hyaluronic acid-uricase multivesicular liposomes,UHMVLs)的体外特性及其在大鼠体内的药效学.方法 采用复乳法制备UHMVLs并测定包封率及理化特性.取12只健康雄性SD大鼠,模型组采用次黄嘌呤和氧嗪酸钾建立高尿酸血症大鼠模型(n=3),UHMVLs组(n=3)和UC组(n=3)分别于建模后尾静脉注射UHMVLs和游离UC,并以正常组(n=3)为对照,测定大鼠血清中尿酸水平.结果 UHMVLs的平均包封率为(62.48±3.87)％ (n=3).UHMVLs和UC最适温度均为40℃,最适pH值分别为8.0和8.5.在同一温度(20～70℃)和pH(6.5～9.5)条件下,UHMVLs中UC的活性均高于游离UC(P＜0.05).除1、36、48 h外,其余各时间点UHMVLs降低高尿酸血症大鼠模型血清中尿酸水平的效果均较游离UC更显著(P＜0.05).结论 在相同条件下,UHMVLs不仅能提高UC的活性,还可以增强UC的稳定性;UHMVLs在大鼠体内降低血尿酸水平的能力优于游离UC.

Characteristics in vitro and preliminary pharmacodynamics of hyaluronic acid-uricase multivesicular liposomes

Objective To investigate the characteristics of hyaluronic acid-uricase multivesicular liposomes (UHMVLs) in vitro and the pharmacodynamics of UHMVLs in rats.Methods UHMVLs was prepared by multiple emulsion method.The entrapment efficiency and physicochemical properties were detected.Twelve healthy male SD rats were enrolled in this study.The rat model of hyperuricemia was established with hypoxanthine and oteracil potassium,while the normal rats (n=3) were set as controls.Intravenous UHMVLs,uricase (UC) and nothing were given to the rats of UHMVLs group (n=3),UC group (n=3) and hyperuricemia model group (n=3),respectively;the levels of serum uric acid (UA) were detected in rats of the 4 groups.Results The average entrapment efficiency of UHMVLs was (62.48±3.87)％.The optimum temperatures of UHMVLs and UC were 40℃,while the optimum pH values of UHMVLs and free UC were 8.0 and 8.5,respectively.The activity of UC in UHMVLs was significantly higher than that in free UC at the same temperature (20-70 ℃) and pH value (6.5-9.5) (P＜0.05).UHMVLs was more effective than free UC in decreasing serum UA in rats with hyperuricemia at all time points (P＜0.05),except for 1 h,36 h and 48 h.Conclusion Under the same condition,UHMVLs can improve not only the activity,but also the stability of UC.UHMVLs is more effective in decreasing serum uric acid in rats compared with free UC,which may pave a way for clinical application of UC.