Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel
1 Department of Veterinary Pharmacology and Toxicology, Konkuk University, Seoul 143-701, Republic of Korea
2 SunBio Inc, Anyang 431-804, Republic of Korea
3 Department of Physiology, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea
4 Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 143-701, Republic of Korea
5 Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA
6 Current address: Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
BMC Cancer 2010, 10:211 doi:10.1186/1471-2407-10-211Published: 18 May 2010
We have studied the in vitro and in vivo utility of polyethylene glycol (PEG)-hydrogels for the development of an anticancer drug 5-fluorouracil (5-FU) delivery system.
A 5-FU-loaded PEG-hydrogel was implanted subcutaneously to evaluate the drug retention time and the anticancer effect. For the pharmacokinetic study, two groups of male rats were administered either an aqueous solution of 5-FU (control group)/or a 5-FU-loaded PEG-hydrogel (treated group) at a dose of 100 mg/kg. For the pharmacodynamic study, a human non-small-cell lung adenocarcinoma (NSCLC) cell line, A549 was inoculated to male nude mice with a cell density of 3 × 106. Once tumors start growing, the mice were injected with 5-FU/or 5-FU-loaded PEG-hydrogel once a week for 4 weeks. The growth of the tumors was monitored by measuring the tumor volume and calculating the tumor inhibition rate (IR) over the duration of the study.
In the pharmacokinetic study, the 5-FU-loaded PEG-hydrogel gave a mean residence time (MRT) of 8.0 h and the elimination half-life of 0.9 h; these values were 14- and 6-fold, respectively, longer than those for the free solution of 5-FU (p < 0.05). In the pharmacodynamic study, A549 tumor growth was significantly inhibited in the 5-FU-loaded PEG-hydrogel group in comparison to the untreated group beginning on Day 14 (p < 0.05-0.01). Moreover, the 5-FU-loaded PEG-hydrogel group had a significantly enhanced tumor IR (p < 0.05) compared to the free 5-FU drug treatment group.
We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.