TISSUE DISTRIBUTION AND ANTI-TUMOR EFFECT OF LIPOSOME-ENTRAPPED DOXORUBICIN (ADRIAMYCIN) IN EHRLICH SOLID TUMOR-BEARING MOUSE

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Abstract
The usefulness of liposomes (in neutral, positively and negatively charged forms) as a carrier for adriamycin (ADM) was studied by examining the distribution of ADM and related fluorescent compounds in Ehrlich solid tumor-bearing mice. The mice were given free or liposome-entrapped ADM i.p. The distribution of ADM and related fluorescent compounds between the administration of the free form and liposome-entrapped form was measured by high performance liquid chromatography; the distribution was dependent on the form of the liposomes. The amounts of ADM and its metabolites in the mouse serum 20 min after administration of neutral-liposome-entrapped ADM were 10 times those after the administration of free ADM, 6 times those after the administration of a negatively charged form and 3.5 times those in the administration of positively charged form. There was no marked difference in the concentrations of these compounds 5 h after administration. The concentration of these compounds in the liver 60 min after administration of each liposome-entrapped form of ADM were in inverse correlation with the concentrations in the serum obtained at 20 min after administration. Total concentrations of ADM and its metabolites in the tumors 20 min after administration of each entrapped form of ADM were 4-5 times that in administration of free ADM after 20 min. There were no marked differences in the concentration of ADM for administration of the various liposome forms. Statistically significant decreases in mean tumor weight were seen in the groups given neutral, positively and negatively charged liposome-entrapped forms compared to corresponding control groups given with free ADM.