THERAPEUTIC EFFICACY OF 5-FLUOROURACIL PRODRUGS USING ENDOGENOUS SERUM-PROTEINS AS DRUG CARRIERS - A NEW STRATEGY IN DRUG-DELIVERY SYSTEM

To establish a novel drug delivery system for 5-fluorouracil (5FU), we have developed a system in which the low-molecular-weight prodrugs of 5FU bound to endogenous serum proteins, thus circulating like those p roteins. Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To examine the therapeutic effect of t hese prodrugs, we injected them into BALB/c mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs, 1-(N-4-chlorop henyl-N-methylcarbamoyl)-5 (5FU-1pCPMC) was effective in reducing tumo rs and prolonging survival time. The non-hydrolyzable compound, 1-(4-c hlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, sugg esting that the therapeutic efficacy of 5FU-1pCPMC is due to the susta ined release of 5FU from the serum protein-prodrug complex. The data s hown here may create a new field in drug delivery system technology.