title: Pharmacokinetic properties and antitumor efficacy of the 5-fluorouracil loaded PEG-hydrogel.
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 x 10(6). 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.
  
  
  CONCLUSIONS
  We suggest that 5-FU-loaded PEG-hydrogels could provide a useful tool for the development of an anticancer drug delivery system.
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Yi
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Cho
authors.forename: Soo-Min
authors.initials: SM
authors.lastname: Cho
authors.forename: Dong-Goo
authors.initials: DG
authors.lastname: Lee
authors.forename: A M
authors.initials: AM
authors.lastname: Abd El-Aty
authors.forename: So-Jeong
authors.initials: SJ
authors.lastname: Yoon
authors.forename: Gun-Won
authors.initials: GW
authors.lastname: Bae
authors.forename: Kwang
authors.initials: K
authors.lastname: Nho
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.forename: Chi-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Jin-Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Michael G
authors.initials: MG
authors.lastname: Bartlett
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Shin
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D020100:Hydrogels; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D004343:Drug Implants; D020100:Hydrogels; D011092:Polyethylene Glycols; D005472:Fluorouracil