Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (BHU), Varanasi, 221005, India.
Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India.
Colloids Surf B Biointerfaces. 2019 Jan 1;173:366-377. doi: 10.1016/j.colsurfb.2018.10.007. Epub 2018 Oct 4.
Breast cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) has led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted as well as targeted nanoparticles were in the range of 126-186 nm and 74-78% respectively. In-vitro studies on SK-BR-3 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional formulation i.e., Docel™. The IC values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than Docel™. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than Docel™. Further, after i.v administration, non-targeted and targeted nanoparticles achieved 3.48 and 5.94 times prolonged half-life in comparison to Docel™. The area under the curve (AUC), relative bioavailability (F) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles when compared to Docel™. The histopathology studies of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney when compared to Docel™.
乳腺癌中，表皮生长因子受体 2（HER-2）的过度表达导致了开发针对 HER-2 的抗癌治疗药物的概念。载紫杉醇的 D-α-生育酚聚乙二醇 1000 琥珀酸接枝壳聚糖（TPGS-g-壳聚糖）纳米粒制备有无曲妥珠单抗修饰。常规、非靶向和靶向纳米粒的粒径和包封效率分别在 126-186nm 和 74-78%的范围内。在 SK-BR-3 细胞的体外研究表明，与常规制剂 Docel™相比，载紫杉醇的非靶向和 HER-2 受体靶向 TPGS-g-壳聚糖纳米粒增强了细胞摄取和细胞毒性，并具有良好的生物黏附特性。细胞毒性试验的 IC 值表明，非靶向和靶向纳米粒的 IC 值分别比 Docel™高 43 倍和 223 倍。体内药代动力学研究表明，与 Docel™相比，非靶向和 HER-2 受体靶向纳米粒的相对生物利用度分别提高了 2.33 倍和 2.82 倍。此外，与 Docel™相比，非靶向和靶向纳米粒在静脉给药后分别延长了 3.48 倍和 5.94 倍的半衰期。与 Docel™相比，曲线下面积（AUC）、相对生物利用度（F）和平均滞留时间（MRT）均较高。非靶向和靶向纳米粒的组织病理学研究表明，与 Docel™相比，它们对肺、肝和肾等重要器官的毒性较小。
