The Disposition of Serum Proteins as Drug-Carriers in Mice Bearing Sarcoma 180

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The tumor distribution and the disposition of serum proteins, such as albumin, fetuin, transferrin, and IgG, were investigated in mice bearing Sarcoma 180. Serum proteins labeled with fluoresceinisothiocyanate (FITC) were administered to the mice. The FITC-labeled proteins acylated with glutaric anhydride were also administered to the mice in order to investigate the effect of chemical modification. The plasma concentration of each glutarylated serum protein was significantly lower, about 15 to 46-fold, in comparison to that of the non-acylated protein at 24 h after administration. The tissue distributions of the glutarylated serum proteins were also decreased compared to those of the non-acylated proteins. Especially, the hepatic distribution of albumin and IgG was significantly reduced with glutarylation. The urinary excretion of albumin and transferrin, and fecal excretion of IgG, were significantly increased with glutarylation. The serum proteins were accumulated effectively in the tumor tissue in mice bearing Sarcoma 180. It was found that the tumor distributions were not impaired by the glutarylation, except involving fetuin. It was suggested, therefore, that the glutarylated serum proteins were valuable for relative tumor-selectivity and might be utilized in a macromolecular carrier system for antitumor drugs.
公益社団法人日本薬学会の論文
1993-12-15