Truncated bFGF-mediated cationic liposomal paclitaxel for tumor-targeted drug delivery: improved pharmacokinetics and biodistribution in tumor-bearing mice

J Pharm Sci. 2011 Mar;100(3):1196-205. doi: 10.1002/jps.22348. Epub 2010 Sep 21.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / blood
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Area Under Curve
  • Cations
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Drug Stability
  • Female
  • Fibroblast Growth Factor 2*
  • Injections, Intravenous
  • Liposomes*
  • Male
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Paclitaxel / administration & dosage*
  • Paclitaxel / blood
  • Paclitaxel / chemistry
  • Paclitaxel / pharmacokinetics*
  • Particle Size
  • Tissue Distribution

Substances

  • Antineoplastic Agents, Phytogenic
  • Cations
  • Liposomes
  • Fibroblast Growth Factor 2
  • Paclitaxel