Physico-chemical and Antitumor Characteristics of High Molecular Weight Prodrugs of Mitomycin C

概要

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High molecular weight derivatives of mitomycin C (MMC) were synthesized by using dextrans of various molecular weights (MMC-D), poly-L-glutamic acid (MMC-PGA), and bovine serum albumin (MMC-BSA) as carrier moieties, and their physico-chemical characteristics and antitumor activities were examined. MMC was liberated from MMC-D in vitro with a half-life of about 24 h regardless of the size of dextran, while the liberation half-lives of MMC-PGA and MMC-BSA were 35.5 h and 20.2 h, respectively. The molecular sizes of conjugates determined by gel filtration chromatography were slightly larger than those of the original carrier molecules. MMC-D showed significant antitumor activities in BDF_1 mice bearing P388 leukemia or B16 melanoma in an i. p.-i. p. system, depending on their molecular sizes ; i. e., higher maximum activity was obtained at lower dose as the molecular weight increased. MMC-PGA exhibited a superior effect against B16 melanoma in spite of its low molecular weight. These observations suggest the existence of some relationship between the physico-chemical properties of carrier moieties and the antitumor activities of the conjugates.
公益社団法人日本薬学会の論文
1982-08-25