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Characterization of 5-FU-loaded PLGA implant. (A) The appearance of 5-FU-implant with 1 mm diameter and 10 mm length. (B) The schematic of 5-FU-implant for 5-FU release and local anticancer effect.In this study, a biodegradable implant composed of poly(lactide co-glycolide) (PLGA) and 5-fluorouracil (5-FU) was fabricated by mold method and used to impede the colon cancer via the local sustained release of 5-FU after transplanting into the peritoneal cavity. To optimize the 5-FU-implant, different factors such type of polymer, polymer-drug ratio, hydrophilic additives and organic solvents were investigated based on in vitro 5-FU release behavior. The optimized 5-FU-implant was subjected to evaluate the capacity of sustained release of 5-FU in vitro and in vivo. In addition, the pharmacokinetics and bio-distribution of 5-FU-implant were also tested in vivo after grafting into the peritoneal cavity in rat. Moreover, different doses of 5-FU-implants were compared against 5-FU injection for their antitumor activity in colon cancer model in nude mice and for their safety in health rat. The results revealed that the optimized 5-FU-implant possessed excellent sustained release of 5-FU for 2 week and no burst release were observed in vitro and in vivo. The pharmacokinetic behavior showed that higher concentration of 5-FU was found in peritoneal fluid when compared to plasma, which resulted in significantly improving antitumor activity as well as decreasing the side effect. It was proved that the 5-FU-implant was more efficacious and much safer than 5-FU bolus injection, which would be also used to overcome the reoccurrence of colon cancer after surgery.