Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes

• DOI: 10.2147/ijn.s33835
• Publication Date: 2012-07-23T04:25:36Z
• Authors: Jingqing Zhang; Tan; Wang; Yang; Li; Xiong; Wu; Zhao; Wang; Yin
• Keywords: Male; Drug Carriers; 0303 health sciences; Urate Oxidase; Hydrogen-Ion Concentration; Hemolysis; Rats; Uric Acid; 3. Good health; Rats, Sprague-Dawley; Kinetics; 03 medical and health sciences; International Journal of Nanomedicine; Enzyme Stability; Animals; Allantoin; Original Research; Candida

Previous studies on various enzymosomes (functional lipid vesicles encapsulating an enzyme) have been mostly carried out in vitro and have focused on preserving catalytic activity and improving the stability of the enzyme. Until now, few studies have focused on their in vivo fate. Similarly, although we have previously reported the increased in vitro uricolytic activity (about 2.2 times higher than that of free uricase, or three times higher than that of PEGylated uricase, Puricase(®), under physiological pH and temperature) and improved stability of the novel alkaline enzymosomes (functional lipid vesicles encapsulating uricase from Candida utilis: uricase-containing lipid vesicles, UOXLVs), it is still necessary to study the biological properties and hypouricemic effects of UOXLVs in vivo.The enzyme kinetics, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary safety of UOXLVs were evaluated.The Michaelis constant (K(m)) value of the UOXLVs was slightly lower than that of the free enzyme. The enzyme release from the UOXLVs lasted over 12 hours and their circulation half-life was about sevenfold longer than that of the free uricase. Meanwhile, the UOXLVs had a 22-fold increase in the area under the curve compared with the free uricase. Furthermore, it took less than 3 hours for the UOXLVs to lower the plasma uric acid concentration from a high to a normal level, compared with 6 hours for the free uricase. In addition, the UOXLVs had much less immunogenicity than free uricase and were well tolerated by all animals throughout the observation period.The UOXLVs markedly improved the biological properties and enhanced the hypouricemic effects of uricase in vivo.