Uricase from Bacillus fastidious loaded in alkaline enzymosomes: Enhanced biochemical and pharmacological characteristics in hypouricemic rats

The aim of this study was to assess the potential of a novel alkaline enzymosome to deliver uricase from Bacillus fastidious (UBF) and enhance its biochemical and pharmacological characteristics. The in vitro catalytic activity of the UBF loaded in the novel alkaline enzymosomes (ESUBFs) was almost 3.8 times that of free UBF at the optimum pH or 1.5 times that of free UBF at the physiological pH. Following intravenous (i.v.) administration (2000 mU/kg) in rats, ESUBFs provided significantly higher (22.5-fold) area under the plasma concentration (AUC) and longer (8.2-fold) circulation half-life (t(1/2)) compared with free UBF, respectively. Further, it took only 4.5 h (or 1.1 h) for ESUBFs to lower the plasma uric acid concentration from a high level to the normal level of rat (or human beings), compared with 7.6 h (or 5.4 h) for free UBF. Our results showed that ESUBFs could efficiently deliver UBF and favorably modify its biochemical and pharmacological characteristics by increasing the AUC, t(1/2), and catalytic activity. Therefore, ESUBFs might be a preferred alternative to cure hyperuricemia and gout. (c) 2012 Elsevier B.V. All rights reserved.