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Publications (1)0 Total impact

  • Yuichiro Kojima, Hiroshi Maeda
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    ABSTRACT: Conjugation of poly(vinyl alcohol) (PVA) containing a thiol group to superoxide dismutase (SOD) was performed by using N-(∈-maleimido caproyloxy)succinimide (EMCS) as a coupling agent. Various chemical charac teristics and pharmacokinetic parameters were evaluated. Two different molec ular weight PVA-SOD conjugates were prepared. Both retained at least 92% of the native SOD activity whereas the plasma half-life increased from 4.8 min for the native SOD to 3.0 and 7.8 h for the low and high molecular weight PVA conjugates, respectively. Tissue distribution studies revealed that in travenously administered PVA-SOD had a high concentration primarily in the circulation, followed by the kidney, the lung, the liver, and the spleen. Un modified SOD was rapidly excreted via the urine, with the exception of high retention in the kidney (36% of the injected dose). PVA-SOD was also rapidly ex creted in the urine, which suggests that the kidney is the main route of excre tion of the derivatives. PVA-SOD exhibited a lower antigenicity and immuno genicity and an enhanced therapeutic effect against ischemic edema of the mouse foot pad compared with the native form. PVA with a thiol functional group appears to be useful for the preparation of protein drug-polymer conju gates, with significant diminution of immunogenicity but retention of almost full biological activity attributable to both mild conjugation conditions and selective reaction.
    Journal of Bioactive and Compatible Polymers - J BIOACT COMPAT POLYM. 01/1993; 8(2):115-131.