Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Department of Pharmaceutics, Indian Institute of Technology (BHU), Varanasi 221005, India.
Mater Sci Eng C Mater Biol Appl. 2017 May 1;74:167-176. doi: 10.1016/j.msec.2017.02.008. Epub 2017 Feb 4.
Brain cancer, up-regulated with transferrin receptor led to concept of transferrin receptor targeted anticancer therapeutics. Docetaxel loaded d-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-chitosan) nanoparticles were prepared with or without transferrin decoration. In vitro experiments using C6 glioma cells showed that docetaxel loaded chitosan nanoparticles, non-targeted and transferrin receptor targeted TPGS-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity. The IC values of non-targeted and transferrin receptor targeted nanoparticles from cytotoxic assay were found to be 27 and 148 folds, respectively higher than Docel™. In vivo pharmacokinetic study showed 3.23 and 4.10 folds enhancement in relative bioavailability of docetaxel for non-targeted and transferrin receptor targeted nanoparticles, respectively than Docel™. The results have demonstrated that transferrin receptor targeted nanoparticles could enhance the cellular internalization and cytotoxicity of docetaxel via transferrin receptor with improved pharmacokinetics for clinical applications.
脑癌中，转铁蛋白受体的上调导致了针对转铁蛋白受体的抗癌治疗的概念。载多西紫杉醇的 d-α-生育酚聚乙二醇 1000 琥珀酸酯接枝壳聚糖（TPGS-壳聚糖）纳米粒是有或没有转铁蛋白修饰制备的。使用 C6 神经胶质瘤细胞进行的体外实验表明，载多西紫杉醇的壳聚糖纳米粒、非靶向和转铁蛋白受体靶向 TPGS-壳聚糖纳米粒增强了细胞摄取和细胞毒性。细胞毒性试验的 IC 值表明，非靶向和转铁蛋白受体靶向纳米粒的 IC 值分别比 Docel™高 27 倍和 148 倍。体内药代动力学研究表明，非靶向和转铁蛋白受体靶向纳米粒的多西紫杉醇相对生物利用度分别比 Docel™提高了 3.23 倍和 4.10 倍。结果表明，转铁蛋白受体靶向纳米粒可通过转铁蛋白受体增强多西紫杉醇的细胞内化和细胞毒性，改善其药代动力学，从而具有临床应用前景。
