Talkar Swapnil S, Kharkar Prachi B, Patravale Vandana B
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, Maharashtra, 400 019, India.
AAPS PharmSciTech. 2020 Oct 25;21(8):295. doi: 10.1208/s12249-020-01839-1.
The current work is focused on the development of docetaxel loaded pomegranate seed oil based lipid nanosystem. Docetaxel loaded pomegranate seed oil nanostructured lipid carriers (DTX-PSO-NLCs) were formulated by the melt emulsification method for parenteral delivery. The developed formulation was characterized in terms of their physicochemical parameters, solid-state characterization, in vitro drug release, in vitro cytotoxicity studies, and in vivo pharmacokinetics and biodistribution studies. Stability studies were carried out as per ICH guidelines Q1A. Melt emulsification method resulted in the formulation of stable DTX-PSO-NLCs with a particle size in the range of 150-180 nm and an entrapment efficiency of 63-65%. The in vitro release showed a slow and sustained release of the drug from the formulation compared to the marketed formulation (i.e., Daxotel®). The formulation was found to be stable for a period of 12 months at conditions of 4°C ± 2°C, 25°C ± 2°C/60% RH ± 5%RH, and 40°C ± 2°C/75% RH ± 5%RH. The developed nanosystem exhibited promising antitumor activity against various types of cancerous cell lines (i.e., MCF7, DU145, U87MG, and NCI-H460) relative to the marketed formulation. The pharmacokinetic evaluation revealed that DTX-PSO-NLCs had a better kinetic profile compared to the marketed formulation. Graphical abstract.
当前的工作聚焦于基于多西他赛负载石榴籽油的脂质纳米系统的开发。采用熔融乳化法制备了用于肠胃外给药的多西他赛负载石榴籽油纳米结构脂质载体（DTX - PSO - NLCs）。所开发的制剂通过其物理化学参数、固态表征、体外药物释放、体外细胞毒性研究以及体内药代动力学和生物分布研究进行表征。稳定性研究按照国际协调会议（ICH）指南Q1A进行。熔融乳化法制备出了稳定的DTX - PSO - NLCs，其粒径在150 - 180纳米范围内，包封率为63 - 65%。与市售制剂（即泰索帝®）相比，体外释放显示该制剂中的药物呈缓慢且持续释放。该制剂在4°C ± 2°C、25°C ± 2°C/60%RH ± 5%RH以及40°C ± 2°C/75%RH ± 5%RH条件下12个月内保持稳定。相对于市售制剂，所开发的纳米系统对多种癌细胞系（即MCF7、DU145、U87MG和NCI - H460）展现出有前景的抗肿瘤活性。药代动力学评估表明，DTX - PSO - NLCs与市售制剂相比具有更好的动力学特征。图形摘要。
