Truncated bFGF-mediated cationic liposomal paclitaxel for tumor-targeted drug delivery: improved pharmacokinetics and biodistribution in tumor-bearing mice.
Truncated bFGF-mediated cationic liposomal paclitaxel for tumor-targeted drug delivery: improved pharmacokinetics and biodistribution in tumor-bearing mice.
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DOI：
10.1002/jps.22348
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发表时间：
2011-03
影响因子：
3.8
通讯作者：
Xianhuo Wang;Linyu Deng;Xiang Chen;Heying Pei;Lulu Cai;Xia Zhao;Yuquan Wei;Li-juan Chen
中科院分区：
文献类型：
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作者：
Xianhuo Wang;Linyu Deng;Xiang Chen;Heying Pei;Lulu Cai;Xia Zhao;Yuquan Wei;Li-juan Chen
成纤维细胞生长因子受体在多种肿瘤细胞表面和肿瘤新生血管上过度表达，是肿瘤和血管靶向治疗的潜在靶点。本研究的目的是比较新型截短型碱性成纤维细胞生长因子多肽介导的阳离子脂质体紫杉醇(tbFGF-LPS-PTX)与游离紫杉醇(F-PTX)和阳离子脂质体紫杉醇(LPS-PTX)在荷瘤小鼠体内的药代动力学和组织分布。在血浆中，tbFGF-LPS-PTX与LPs-PTX具有相似的药代动力学特性，但与F-PTX不同。AUC(0→∞)分别是F-PTX和LPS-PTX的1.38倍和1倍。与其他两种剂型相比，TbFGF-LPS-PTX的生物分布特征有显著差异，在肿瘤和脾组织中有较高的蓄积。与F-→∞和LPS-PTX相比，AUC(0PTX)在肿瘤中的蓄积分别增加约7.17倍和2.6倍，在脾中的蓄积分别增加约4.28倍和2.25倍。肝脏AUC(0→∞)值明显低于F-Ptx和Lps-Ptx。结果表明，tbFGF-LPS-PTX可显著增加肿瘤内药物的蓄积，延长药物在肿瘤中的滞留时间，是一种很有前途的肿瘤靶向给药系统，有望为肿瘤的治疗提供新的策略。
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.