In vivo distribution of 5-Fluorouracil after peritumoral implantation using a biodegradable micro-device in tumor-bearing mice.

A novel implantable micro-device was used for delivery of 5-Fluorouracil (5-Fu), which was often used in the treatment of various human malignancies. The biodegradable poly(lactic-co-glycolic) acid (PLGA) was used as material. The purpose of this study was to investigate the efficiency of delivery of 5-Fu to the tumor via this delivery system. The distribution characters of the 5-Fu in tumor, plasma, peritumoral tissue, liver and kidney were compared after peritumoral implantation of micro-device and intraperitoneal injection of solution. After administration of micro-device, the 5-Fu was absorbed into the tumor on Day 1, and Cmax (4.14 μg/g) was reached on Day 6. The half life for the elimination was 4.48 d and the AUC was 46.78 μg × d/g. Similar pharmacokinetic behaviors were observed in plasma, peritumoral tissue, kidney and liver, while the Cmax and the AUC of plasma and these tissues were lower than those of tumor. When administered the solution, 5-Fu was rapidly absorbed into plasma, liver, kidney, spleen and tumor, and rapidly cleared from these tissues after 2 or 4 h. And the AUC in tumor of 5-Fu solution was significantly lower than that of the micro-device. These results indicated that 5-Fu loaded biodegradable micro-device offered a relatively high concentration and long-term delivery of the drug to the tumor site.