In vitroandin vivoevaluation of injectable implants for intratumoral delivery of 5-fluorouracil

The aim of this study was to evaluate poly (ε-caprolactone) (PCL)-based injectable implants, which could achieve sustained release of 5-fluorouracil (5-FU) directly to tumors. The implants were prepared by injection molding and the effects of drug loading and poly (ethylene glycol) (PEG) as additive on drug release were investigated. Two implants (PCL/5-FU25% and PCL/PEG5%/5-FU25%) were selected for in vivo evaluation regarding drug distribution in tumor, plasma concentration and antitumor effect. In vitro release test showed that drug release duration varied from 18 to 565 h depending on the compositions of the implant. After intratumoral injection, in vivo release of 5-FU from implants PCL/5-FU25% and PCL/PEG5%/5-FU25% were apparently accelerated. The maximum drug concentrations in tumor were sevenfold and ninefold higher than that attained by intraperitoneal (i.p.) administration of 5-FU solution for the implants PCL/5-FU25% and PCL/PEG5%/5-FU25%, respectively. Drug concentration in plasma was always below 0.1 μg/ml over the entire experimental period. Additionally, the two implants exhibited better tumor growth inhibition as shown by the results that their tumor volumes were approximately twofold smaller than those treated by i.p. administration after 7 days. The present study demonstrated that the injectable 5-FU-loaded implants could minimize drug systemic exposure and exert desirable antitumor activity.