title: Peptide ligand and PEG-mediated long-circulating liposome targeted to FGFR overexpressing tumor in vivo.
abstract: METHODS
  Paclitaxel, a widely used antitumor agent, has limited clinical application due to its hydrophobicity and systemic toxicity. To achieve sustained and targeted delivery of paclitaxel to tumor sites, liposomes composed of egg phosphatidylcholine, cholesterol, and distearolyphosphatidyl ethanolamine-N-poly(ethylene glycol) (PEG(2000)) were prepared by a lipid film method. In addition, the liposomes also contained truncated fibroblast growth factor fragment-PEG-cholesterol as a ligand targeting the tumor marker fibroblast growth factor receptor. Physicochemical characteristics, such as particle size, zeta potential, entrapment efficiency, and release profiles were investigated. Pharmacokinetics and biodistribution were evaluated in C57BL/6 J mice bearing B16 melanoma after intravenous injection of paclitaxel formulated in Cremophor EL (free paclitaxel), conventional liposomes (CL-PTX), or in targeted PEGylated liposomes (TL-PTX).
  
  
  RESULTS
  Compared with CL-PTX and free paclitaxel, TL-PTX prolonged the half-life of paclitaxel by 2.01-fold and 3.40-fold, respectively, in plasma and improved the AUC(0→t) values of paclitaxel by 1.56-fold and 2.31-fold, respectively, in blood. Biodistribution studies showed high accumulation of TL-PTX in tumor tissue and organs containing the mononuclear phagocyte system (liver and spleen), but a considerable decrease in other organs (heart, lung, and kidney) compared with CL-PTX and free paclitaxel.
  
  
  CONCLUSIONS
  The truncated fibroblast growth factor fragment-conjugated PEGylated liposome has promising potential as a long-circulating and tumor-targeting carrier system.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Cai
authors.forename: Xianhuo
authors.initials: X
authors.lastname: Wang
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.forename: Neng
authors.initials: N
authors.lastname: Qiu
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Wen
authors.forename: Xingmei
authors.initials: X
authors.lastname: Duan
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qian
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001665:Binding Sites; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011897:Random Allocation; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D008081:Liposomes; D010455:Peptides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D017468:Receptors, Fibroblast Growth Factor; C038089:1,2-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D002784:Cholesterol; D017239:Paclitaxel