Biochemical and biopharmaceutical properties of macromolecular conjugates of uricase with dextran and polyethylene glycol.
Uricase (UC) was conjugated with dextran and polyethylene glycol and their biochemical and biopharmaceutical properties were studied. UC-dextran conjugates (UC-D) synthesized by four methods, periodate oxidation, cyanogen bromide, carbodiimide and cyanuric chloride largely retained the UC enzymatic activity depending on the extent to which they modified amino groups. The periodate oxidation method seemed best because it gave a conjugate with high yield and satisfactory activity retention. The conjugate of UC with activated polyethylene glycol (UC-PEG2) was also obtained with high yield but the remaining activity was somewhat lower than those of dextran conjugates at the same modification extent. UC-D and UC-PEG2 showed sustained enzymatic activity in plasma after intravenous injection to rats. The advantage of chemical modification of proteins, especially with dextran, by the periodate oxidation method for preparation of a protein-delivery system was thus suggested.
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Y
Y
Yasuda
T
T
Fujita
Y
Y
Takakura
M
M
Hashida
H
H
Sezaki
D000818:Animals; D001702:Biopharmaceutics; D003911:Dextrans; D004355:Drug Stability; D008297:Male; D011092:Polyethylene Glycols; D051381:Rats; D011919:Rats, Inbred Strains; D014503:Urate Oxidase / Q000276:immunology / Q000378:metabolism* / Q000493:pharmacokinetics
D003911:Dextrans; D011092:Polyethylene Glycols; D014503:Urate Oxidase