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

摘要

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-->infinity) 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-->infinity) 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-->infinity) 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.