Abstract
Development of anticancer drugs provides the significant achievement in the clinical treatment. However most of the clinical antitumor drugs have severe side effects such as leukocytepenta. To reduce side effects and enhance antitumor activity, the delivery of antitumor reagent should be controlled. One of the most effective methods to control the pharmacokinetics is the conjugation of antitumor drugs with polymeric carriers. We have developed novel conjugates of DIVEMA (copolymer of divinyl ether and maleic anhydride) with anticancer drugs (adriamycin and methotrexate) and cytokine (TNF-α). The conjugates proved to have more effective than anticancer drugs against murine cancer models including solid tumors with less toxicity. Such polymeric conjugates proved to be effective to improve the body distribution of bioactive proteins, which are quickly hydrolyzed by proteolytic enzymes in vivo. As a model of protein, we have examined the anti-inflammatory activity of the conjugated of SOD (superoxide dismutase) with DIVEMA. Liver resection and liver transplantation needs the effective protection of ischemia-reperfusion injury, which leads to organ failure. Some attempts have been made for protect ischemia-reperfusion injury by means of SOD. Due to the short half-life in vivo of SOD alone (less than 5 min), the clinical effectiveness of SOD was quite limited. Through dynamic observation of the liver microcirculation using intra-vital microscopy techniques, we have evaluated the effect of DIVEMA-SOD on ischemia-reperfusion liver injury. DIVEMA-SOD showed protective effect of ischemia-reperfusion injury significantly as compared to SOD alone. The copolymer of DIVEMA provides the possibility for great achievement of with cytokines, and organ protection in the transplantation medicine.
