Abstrakt

In vivo biodistribution for tumor targeting of 5-fluorouracil (5-FU) loaded N-succinyl-chitosan (Suc-Chi) nanoparticles

Yan Chengyun, Gu Jiwei, Cheng Yan, Huang Zhan, Chen Dawei

5-fluorouracil-loaded N-succinyl-chitosan nanoparticles (5-FU-Suc-Chi/NP) were prepared by an emulsification solvent diffusion. Biodistribution and tumor targeting were evaluated after i.v. administration of 5-Fu-Suc-Chi/ NPs in Sarcoma 180-bearingmice.Also, pharmacokinetic profileswere evaluated after intravenous injection of 5-Fu-Suc-Chi/NP via the tail vein to rats. Our experimental results showed the 5-FU-Suc-Chi/NPs could be sustained at a high level in blood throughout a very long time, implying its long systemic retention in blood circulation. 5-FU-Suc-Chi/NPswere distributed mainly in tumor, liver and a small quantity of 5-FU-Suc-Chi-NPswas found in kidney and speen. 5-FU-Suc-Chi/NPs scarcely accumulated in the heart and lung, lowered the toxic effect of 5-FU to them. Pharmacokinetic analysis in plasma showed area under plasma concentration-time curve(AUC), elimination half-life (t1/2) and residence time (MRT)were increased 2.5-fold, 10.98- fold and 10.8-fold for 5-FU-Suc-Chi/NP compared with that of free 5-FU, respectively. All the results indicates that longevity in blood circulation and tumor targeting of 5-FU-Suc-Chi/NPs should be achieved.