Truncated bFGF-mediated cationic liposomal paclitaxel for tumor-targeted drug delivery: improved pharmacokinetics and biodistribution in tumor-bearing mice.
Fibroblast growth factor receptors, overexpressed on the surface of a variety of tumor cells and on tumor neovasculature, are potential targets for tumor- and vascular-targeting therapy. The purpose of our present study was to compare the pharmacokinetics and tissue distribution of a novel truncated basic fibroblast growth factor peptide-mediated cationic liposomal paclitaxel (tbFGF-LPs-PTX) with free paclitaxel (F-PTX) and cationic liposomal paclitaxel (LPs-PTX) in tumor-bearing mice. In plasma, tbFGF-LPs-PTX exhibited similar pharmacokinetic properties to LPs-PTX but different with F-PTX. The AUC(0→∞) values were about 1.38-fold and one fold compared with those of F-PTX and LPs-PTX, respectively. TbFGF-LPs-PTX showed significant difference in biodistribution characteristics and displayed high accumulation in tumor and spleen in comparison with other two formulations. The AUC(0→∞) values achieved, respectively, about 7.17-fold and 2.60-fold accumulation in tumor, and about 4.28-fold and 2.25-fold increase in spleen compared with those of F-PTX and LPs-PTX. In contrast, the AUC(0→∞) values were much lower in liver compared with those of F-PTX and LPs-PTX. Our data indicated that tbFGF-LPs-PTX significantly increased the accumulation in tumor and prolonged the retention time, suggesting that it was a promise tumor-targeted delivery system and might provide a new treatment strategy for tumors.
Wang
Xianhuo
X
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Deng
Linyu
L
Chen
Xiang
X
Pei
Heying
H
Cai
Lulu
L
Zhao
Xia
X
Wei
Yuquan
Y
Chen
Lijuan
L
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002412:Cations; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D016222:Fibroblast Growth Factor 2; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D002412:Cations; D008081:Liposomes; D016222:Fibroblast Growth Factor 2; D017239:Paclitaxel