Agrawal Poornima, Singh Rahul Pratap, Sharma Gunjan, Mehata Abhishesh K, Singh Sanjay, Rajesh Chellapa V, Pandey Bajarangprasad L, Koch Biplob, Muthu Madaswamy S
Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
Genotoxicology and Cancer Biology Lab, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Colloids Surf B Biointerfaces. 2017 Apr 1;152:277-288. doi: 10.1016/j.colsurfb.2017.01.021. Epub 2017 Jan 15.
The aim of this work was to prepare targeted bioadhesive d-α- tocopheryl glycol succinate 1000 (TPGS) micelles containing docetaxel (DTX) for brain targeted cancer therapy. Considering the unique bioadhesive feature of chitosan, herein, we have developed a synergistic transferrin receptor targeted bioadhesive micelles using TPGS conjugated chitosan (TPGS-chitosan), which target the overexpressed transferrin receptors of glioma cells for brain cancer therapy. The micelles were prepared by the solvent casting method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release. The IC values demonstrated transferrin receptor targeted TPGS-chitosan micelles could be 248 folds more effective than Docel™ after 24h treatment with the C6 glioma cells. Further, time dependent bioadhesive cellular uptake study indicated that a synergistic effect was achieved with the chitosan and transferrin in targeted TPGS-chitosan micelles through the biodhesive property of chitosan as well as transferrin receptor mediated endocytosis. The in-vivo pharmacokinetic results demonstrated that relative bioavailability of non-targeted and targeted micelles were 2.89 and 4.08 times more effective than Docel™ after 48h of treatments, respectively.
本研究的目的是制备含有多西他赛（DTX）的靶向生物黏附性琥珀酸二-α-生育酚聚乙二醇1000（TPGS）胶束，用于脑靶向癌症治疗。考虑到壳聚糖独特的生物黏附特性，在此，我们使用TPGS共轭壳聚糖（TPGS-壳聚糖）开发了一种协同转铁蛋白受体靶向生物黏附性胶束，其靶向胶质瘤细胞中过表达的转铁蛋白受体用于脑癌治疗。通过溶剂浇铸法制备胶束，并对其粒径、多分散性、zeta电位、表面形态、药物包封率和体外释放进行表征。IC值表明，在用C6胶质瘤细胞处理24小时后，转铁蛋白受体靶向的TPGS-壳聚糖胶束的有效性可能比多西他赛注射剂（Docel™）高248倍。此外，时间依赖性生物黏附细胞摄取研究表明，通过壳聚糖的生物黏附特性以及转铁蛋白受体介导的内吞作用，在靶向TPGS-壳聚糖胶束中壳聚糖和转铁蛋白实现了协同效应。体内药代动力学结果表明，在治疗48小时后，非靶向和靶向胶束的相对生物利用度分别比多西他赛注射剂（Docel™）高2.89倍和4.08倍。
