Department of Thoracic Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, PR China.
Drug Deliv. 2010 Jan;17(1):28-37. doi: 10.3109/10717540903508953.
The study described the development of lipid vesicles as colloidal carriers for uricase, an enzyme with low activity at physicological conditions and low stability in vitro and in vivo. The lipid vesicles containing uricase (UOXLVs) were prepared and the process parameters were optimized with the indexes of entrapment efficiency, polydispersion, particle size, and zeta potential. The storage stability of uricase in lipid vesicles was significantly increased compared to that of free uricase at 4°C. The stability to proteolytic digestion was also increased obviously by entrapping the uricase in the lipid vesicles. In vitro and in vivo pharmacodynamic studies on the hyperuricemia rat model explicitly suggested that the uricase entrapped by UOXLVs possessed high uricolytic activity and distinctively decreased the uric acid level.
本研究描述了脂质体作为尿酸酶的胶体载体的发展，尿酸酶在生理条件下活性较低，体外和体内稳定性也较低。制备了含尿酸酶的脂质体（UOXLVs），并通过包封效率、多分散性、粒径和 Zeta 电位等指标对工艺参数进行了优化。与游离尿酸酶相比，尿酸酶在脂质体中的储存稳定性在 4°C 时显著提高。通过将尿酸酶包封在脂质体中，其对蛋白水解消化的稳定性也明显提高。在高尿酸血症大鼠模型的体外和体内药效学研究中，明确表明 UOXLVs 包封的尿酸酶具有较高的尿酸裂解活性，明显降低了尿酸水平。
