Pharmaceutics Research Laboratory, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilaspur, 495 009, India.
Nanomedicine and Bioengineering Research Laboratory, Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, MP, 4848487, India.
AAPS PharmSciTech. 2020 Jun 16;21(5):174. doi: 10.1208/s12249-020-01690-4.
Hepatocellular carcinoma (HCC) is a foremost type of cancer problem in which asialoglycoprotein receptors are overexpressed. In this study, asialoglycoprotein receptor-targeted nanoformulation (galactose-conjugated TPGS micelles) loaded with docetaxel (DTX) was developed to achieve its site-specific delivery for HCC therapy. The pharmaceutical characteristics like shape morphology, average particle size and zeta potential, drug entrapment efficiency, and in vitro release kinetics of developed system were evaluated. DTX-loaded galactosylated TPGS (DTX-TPGS-Gal) micelles and TPGS micelles (DTX-TPGS) were having 58.76 ± 1.82% and 54.76 ± 1.42% entrapment of the DTX, respectively. In vitro drug release behavior from micelles was controlled release. Cytotoxicitiy (IC) of DTX-TPGS-Gal formulation on HepG2 cell lines was significantly (p ≤ 0.01) lower (6.3 ± 0.86 μg/ml) than DTX-TPGS (9.06 ± 0.82 μg/ml) and plain DTX (16.06 ± 0.98 μg/ml) indicating higher efficacy of targeted formulation. Further, in vivo biodistribution studies in animal model showed maximum drug accumulation at target site, i.e., the liver in the case of DTX-TPGS-Gal as compared with non-targeted one. It is concluded from the findings that TPGS-Gal micelles can be utilized for targeted drug delivery of cytotoxic drugs towards HCC with minimized side effects. Graphical abstract.
肝细胞癌（HCC）是一种主要的癌症问题，其中唾液酸糖蛋白受体过表达。在这项研究中，开发了一种靶向去唾液酸糖蛋白受体的纳米制剂（半乳糖偶联 TPGS 胶束），用于载多西紫杉醇（DTX），以实现其对 HCC 治疗的靶向递药。对所开发系统的制剂特性（如形态学、平均粒径和 Zeta 电位、药物包封效率和体外释放动力学）进行了评价。载多西紫杉醇的半乳糖化 TPGS（DTX-TPGS-Gal）胶束和 TPGS 胶束（DTX-TPGS）的 DTX 包封率分别为 58.76±1.82%和 54.76±1.42%。胶束的体外药物释放行为呈控制释放。DTX-TPGS-Gal 制剂对 HepG2 细胞系的细胞毒性（IC）显著（p≤0.01）低于 DTX-TPGS（9.06±0.82μg/ml）和普通 DTX（16.06±0.98μg/ml），表明靶向制剂的疗效更高。此外，在动物模型中的体内生物分布研究表明，与非靶向制剂相比，DTX-TPGS-Gal 在靶部位（即肝脏）的药物积累最大。从研究结果可以得出结论，TPGS-Gal 胶束可用于载有细胞毒性药物的靶向药物递送，以降低副作用。
