Oku N, Yamashita S, Sakuragi N, Doi K, Okada S, Shimidzu K, Sumi M, Nadai T, Kusumoto S, Suda Y
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Biol Pharm Bull. 1995 Jan;18(1):181-4. doi: 10.1248/bpb.18.181.
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 proteins. Subsequently, the prodrugs were slowly hydrolyzed to generate active 5FU in the bloodstream. To examine the therapeutic effect of these prodrugs, we injected them into BALB/c mice previously implanted subcutaneously with Meth A sarcoma. Among the prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)-5-fluorouracil (5FU-1pCPMC) was effective in reducing tumors and prolonging survival time. The non-hydrolyzable compound, 1-(4-chlorobenzyl)-5-fluorouracil, did not show any therapeutic effect, suggesting that the therapeutic efficacy of 5FU-1pCPMC is due to the sustained release of 5FU from the serum protein-prodrug complex. The data shown here may create a new field in drug delivery system technology.
为建立一种用于5-氟尿嘧啶（5FU）的新型药物递送系统，我们开发了一种系统，其中5FU的低分子量前药与内源性血清蛋白结合，从而像那些蛋白一样循环。随后，前药缓慢水解以在血液中产生活性5FU。为了检查这些前药的治疗效果，我们将它们注射到先前皮下植入Meth A肉瘤的BALB/c小鼠体内。在前药中，1-(N-4-氯苯基-N-甲基氨基甲酰基)-5-氟尿嘧啶（5FU-1pCPMC）在减少肿瘤和延长存活时间方面有效。不可水解的化合物1-(4-氯苄基)-5-氟尿嘧啶没有显示出任何治疗效果，这表明5FU-1pCPMC的治疗效果归因于5FU从血清蛋白-前药复合物中的持续释放。此处所示的数据可能会在药物递送系统技术中开创一个新领域。
