Characteristics in vitro and preliminary pharmacodynamics of hyaluronic acid-uricase multivesicular liposomes / 第二军医大学学报

ABSTRACT

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.