Seki T, Kawaguchi T, Endoh H, Ishikawa K, Juni K, Nakano M
Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.
J Pharm Sci. 1990 Nov;79(11):985-7. doi: 10.1002/jps.2600791108.
Poly-L-lactic acid (MW 6000) microspheres (PLA-MS) containing 5-fluoro-2'-deoxyuridine (FUdR) or four ester prodrugs of FUdR were prepared and examined with regard to the in vitro release kinetics. The incorporation efficiency of the lipophilic prodrugs into the PLA-MS was higher than that of FUdR or the hydrophilic prodrugs. The release of the lipophilic FUdR prodrugs from PLA-MS was sustained as compared with that of FUdR from PLA-MS. The release kinetics of the FUdR prodrugs appears to fit the Higuchi, Baker, and Lonsdale model in the early stage of the release process. The slope of the Baker and Lonsdale plots of the release of divaleryl-FUdR from PLA-MS decreased as the initial drug loading was decreased. The order of the release rates of FUdR prodrugs from PLA-MS with the same prodrug content was similar to that of the water solubilities of the prodrugs. These results suggest that the ester prodrugs could be released from PLA-MS by diffusion through water-filled capillaries or a series of pores rather than by diffusion through the PLA matrix.
制备了含有5-氟-2'-脱氧尿苷（FUdR）或四种FUdR酯前药的聚-L-乳酸（分子量6000）微球（PLA-MS），并对其体外释放动力学进行了研究。亲脂性前药掺入PLA-MS的效率高于FUdR或亲水性前药。与PLA-MS中FUdR的释放相比，亲脂性FUdR前药从PLA-MS中的释放是持续的。在释放过程的早期，FUdR前药的释放动力学似乎符合Higuchi、Baker和Lonsdale模型。随着初始药物负载量的降低，PLA-MS中双戊酰-FUdR释放的Baker和Lonsdale图的斜率减小。具有相同前药含量的PLA-MS中FUdR前药的释放速率顺序与前药的水溶性顺序相似。这些结果表明，酯前药可以通过充满水的毛细管或一系列孔扩散从PLA-MS中释放出来，而不是通过PLA基质扩散释放。
