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Open Access Research article

Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel

Hee Yi1, Hee-Jung Cho1, Soo-Min Cho1, Dong-Goo Lee1, AM Abd El-Aty16, So-Jeong Yoon2, Gun-Won Bae2, Kwang Nho2, Bokyung Kim3, Chi-Ho Lee4, Jin-Suk Kim1, Michael G Bartlett5 and Ho-Chul Shin1*

Author Affiliations

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

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BMC Cancer 2010, 10:211  doi:10.1186/1471-2407-10-211

Published: 18 May 2010

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.