Research on PEG modification of uricase / 中国药科大学学报
Journal of China Pharmaceutical University
;
(6): 557-562, 2008.
Article
Dans Chinois
| WPRIM
| ID: wpr-434150
ABSTRACT
To modify uricase with PEG reagent in order to decrease uricase immunogenieity and increase its stability.Methods:
The branched PEG of 40 kD was chosen to modify native uricase.The properties of the mod-ified uricase including the stabilities to protease,pH and temperature,in vivo half-life time,as well as the immu-nogenicity were evaluated.The pharmacokinetic profiles of the midofied uricase were studied in mice.Results:
It is demonstrated that the conjugation of PEG to lysine residues of Candida utilis uricase resulted in higher tryp-sin resistance.reduced immune response.and prolonged in vivo half-life.PEG modified uricase retained 80% of the enzymatic activity of native uricase.In addition,it was found that half-life in serum of the intravenously injec-ted PEGylated uriease of up to 696 min was longer that that of native uficase of 45 min.Higher plasma drug con-centrations were also reached with dosing of the PEGylated uricase to mice.Furthermore,the binding affinity Was shown to be reduced for the PEG-uricase using ELISA assay.and it was one-eishth that of native uricase.Final-ly,it Was indicated that the PEG uficase induced a delayed immunoresponse in mice following repeated adminis-trations.Conclusion:
These findings demonstrate that this chemically modified form of uricase may serve as a potentially effective drug to treat gout patients.
Texte intégral:
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Indice:
WPRIM (Pacifique occidental)
langue:
Chinois
Texte intégral:
Journal of China Pharmaceutical University
Année:
2008
Type:
Article
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