Synthesis and properties of poly[N-(2-hydroxypropyl) methacrylamide]conjugates of superoxide dismutase

摘要

The synthesis ofN-(2-hydroxypropyl)methacrylamide (HPMA) copolymers and semi-telechelic polymers (HPMA) conjugates superoxide dismutase (SOD) is described.The polymer was conjugated with SOD by means of nondergradable or degradable oligopeptide spacers randomly distributed along the polymer backbone.A second type of conjugation,to a semi-telechelic polymer,poly(HPMA),(PHPMA) containing reactive chain end groups,with the SOD amino groups formed star structures.Phyiscochemical properties of the conjugates,such as temperature stability and stability to oxidation with hydrogen peroxide,were studied and compared tonative SOD;an increase in temperature stability by the conjugates and an increase in stability towards oxidationw ith hydrogen peroxide was observed.The in vivobiological evaluation of PHPMA-SOD conjugates showed a significant decrease in innunogenicity compared to free SOD.A preliminary in vivo study of ischemic/reperfusion injury,revealed significantly more pronounced protective effects by PHPMA-SOD conjugates in comparison with the free SOD.