Construction and assessment for immunogenicity and bioactivity of novel recombinant urate oxidase modified with PEG
- Author:
Jia-Hui ZHANG
1
Author Information
- Publication Type:Journal Article
- Keywords: Gout; Hyperuricemia; Immunogenicity; PEGylation; Recombinant urate oxidase (rUOX); Y-shape PEG succinimidyl propionate
- From: Chinese Pharmaceutical Journal 2014;49(12):1045-1050
- CountryChina
- Language:Chinese
- Abstract: OBJECTIVE: To construct and evaluate the stability, and in vitro bioactivity for new Y-shape PEG-labeled recombinant mammalian urate oxidase rUOX-mPEg as well as pharmacokinetics and immunogenicity compared with the line-shape rUOX-mPEG in rats. METHODS: Physicochemical characteristics and modification degree of PEG were detected by gel electrophoresis and HPLC, bio-activity by enzyme-spectrophotometric method, and immunogenicity though ELISA. Pharmacokinetic and tolerability property were assessed in vivo. RESULTS: The novel Y-shape PEG modified urate oxidase rUOX-mPEG2 presented higher molecular weight, modification degree of PEG compared to line-shape rUOX-mPEG And pharmacokinetic assay showed that rUOX-mPEG2 more excellent curative effects in vivo. Plus, the results of experimental on immunogenicity indicated that the Y-shape PEG modified urate oxidase could reduce immunogenicity effectively. CONCLUSION: The bioavailability, efficacy and stability of rUOX-mPEG2 were greater than those of line-shape rUOX-mPEG and recombinant mammalian control. Bioavailability, efficacy, and tolerability were also superior to that of line-shape and PEG-free urate oxidase. The determination of oxidase pharmacokinetic parameters revealed the linearity kinetic characteristic of rUOX-mPEg implying its potential excellent clinical supplication.
