title: Pharmacokinetic characteristics and anticancer effects of 5-fluorouracil loaded nanoparticles.
abstract: BACKGROUND
  It is expected that prolonged circulation of anticancer drugs will increase their anticancer activity while decreasing their toxic side effects. The purpose of this study was to prepare 5-fluorouracil (5-FU) loaded block copolymers, with poly(gamma-benzyl-L-glutamate) (PBLG) as the hydrophobic block and poly(ethylene glycol) (PEG) as the hydrophilic block, and then examine the 5-FU release characteristics, pharmacokinetics, and anticancer effects of this novel compound.
  
  
  METHODS
  5-FU loaded PEG-PBLG (5-FU/PEG-PBLG) nanoparticles were prepared by dialysis and then scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to observe the shape and size of the nanoparticles, and ultraviolet spectrophotometry was used to evaluate the 5-FU in vitro release characteristics. The pharmacokinetic parameters of 5-FU/PEG-PBLG nanoparticles in rabbit plasma were determined by measuring the 5-FUby high-performance liquid chromatography (HPLC). To study in vivo effects, LoVo cells (human colon cancer cell line) or Tca8113 cells (human oral squamous cell carcinoma cell line) were implanted in BALB/c nude mice that were subsequently treated with 5-FU or 5-FU/PEG-PBLG nanospheres.
  
  
  RESULTS
  5-FU/PEG-PBLG nanoparticles had a core-shell spherical structure with a diameter of 200 nm and a shell thickness of 30 nm. The drug loading capacity was 27.1% and the drug encapsulation was 61.5%. Compared with 5-FU, 5-FU/PEG-PBLG nanoparticles had a longer elimination half-life (t1/2, 33.3 h vs. 5 min), lower peak concentration (C, 4563.5 microg/L vs. 17047.3 microg/L), and greater distribution volume (VD, 0.114 L vs. 0.069 L). Compared with a blank control, LoVo cell xenografts and Tca8113 cell xenografts treated with 5-FU or 5-FU/PEG-PBLG nanoparticles grew slower and had prolonged tumor doubling times. 5-FU/PEG-PBLG nanoparticles showed greater inhibition of tumor growth than 5-FU (p < 0.01). In the PEG-PBLG nanoparticle control group, there was no tumor inhibition (p > 0.05).
  
  
  CONCLUSIONS
  In our model system, 5-FU/PEG-PBLG nanoparticles changed the pharmacokinetic behavior of 5-FU, thus increasing its anticancer activity. 5-Fluorouracil loaded nanoparticles have potential as a novel anticancer drug that may have useful clinical applications.
authors.affiliation: Department of Medicine, Tumor Hospital, Sun Yat-sen University, Guangzhou, China. lisusu@tom.com
authors.forename: Su
authors.initials: S
authors.lastname: Li
authors.forename: Anxun
authors.initials: A
authors.lastname: Wang
authors.forename: Wenqi
authors.initials: W
authors.lastname: Jiang
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Guan
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000648:ultrastructure; D045744:Cell Line, Tumor / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000648:ultrastructure; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000648:ultrastructure; D053758:Nanoparticles / Q000032:analysis / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil