Antitumor activity of lipophilic prodrugs of mitomycin C entrapped in liposome or O/W emulsion.

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Abstract
Nine lipophilic 1a-N-substituted prodrugs of mitomycin C were formulated in lipid dispersion dosage forms and their fundamental antitumor activities were evaluated. The prodrugs were efficiently incorporated into liposome or O/W oil/water emulsion according to their increased lipophilicities, while mitomycin C was hardly entrapped into them. Almost complete incorporation was observed in nonloxycarbonyl and cholesteryloxycarbonyl mitomycin C which showed partition coefficients over 8000 in chloroform/water system. The release rate from these dosage forms determined by a dynamic dialysis method decreased with an increase in the partition coefficients of the derivatives. All prodrugs entrapped in liposome or O/W emulsion showed significant antitumor activities against L1210 mouse leukemia in i.p.-i.p. system except for cholesteryloxycarboxyl mitomycin C. In spite of considerable antitumor activities shown in the forms of liposomes and emulsion, saline suspension of nonloxycarbonyl mitomycin C failed to exhibit any activity because of its poor aqueous solubility. The utility of the combining delivery system of lipophilic prodrug with a physical device such as liposome and O/W emulsion is discussed.