产朊假丝酵母尿酸酶纳米脂质体的研制及其理化性质

Preparation and Characterization of Uricase Loaded in Lipid Nanoparticles

目的研制产朊假丝酵母尿酸酶纳米脂质体(nanoliposomes containing uricase from candida utilis,UCCNLs)并对其理化性质和体外活性进行评价。方法采用逆向蒸发法制备UCCNLs,以包封率、最小多分散指数、粒径等为评价指标优化制备工艺。考察体外降尿酸活性。考察4,25℃纳米粒的稳定性。结果醚水比为3∶1,脂醇比为1∶1,投药量为2 mg时,UCCNLs的平均包封率为64.24%,平均粒径为206.73 nm,多分散系数为0.247,Zeta电位为-37.33 mV。将尿酸从0.595 mol.L-1降至正常水平UCCNLs所需时间约为游离酶的一半。UCCNLs在4℃时具有良好的稳定性。结论采用逆向蒸发法可制备UCCNLs,工艺简便,包封率高,稳定性较好,体外降尿酸效果好。

OBJECTIVE To prepare lipid nanoparticles containing uricase from candida utilis（UCCLNs）and to investigate their properties. METHODS UCCLNs were prepared by reverse-phase evaporation method. The entrapment efficiency, polydispersity index, size, and et al. were set as evaluation indexes for optimizing preparation methods. Uricolytie activity in vitro and the stability of drug loaded lipid nanoparticles were investigated. RESULTS The best formula for UCCLNS was as follows ： the volume ratio of dieth- yl ether and buffer was 3：1 ; the molar ratio of phosphatidylcholine and cholesterol 1： 1 ; and the uriease amount 2 mg. The entrapment efficiency was 64. 24% , average particle size was 206. 73 nm, and Zeta potential was -37. 33 inV. Compared with native uriease solution, it took about a half time for decreasing uric acid from 0. 595 mmol · L- 1 to normal level when the same dosage of UCCLNs were given. UCCLNs were stable under storage conditions. CONCLUSION UCCLNs can be prepared by reverse-phase evaporation method, with the advantages of simple process, small diameter and polydispersity, high encapsulation ratio, good stability and high urieolytic activity.