Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
Department of Mechanical Engineering, Imperial College London, South Kensington Campus, London, UK.
J Pharm Sci. 2019 May;108(5):1736-1745. doi: 10.1016/j.xphs.2018.12.002. Epub 2018 Dec 12.
Surface-modified poly(d,l-lactic-co-glycolic acid) PLGA nanoparticles (NPs) were fabricated via nanoprecipitation for obtaining therapeutic concentration of paclitaxel (PTX) in brain tumor. The cellular uptake and cytotoxicity of NPs were evaluated on C6 glioma cells in vitro, and BALB/c mice were used to study the brain penetration and biodistribution upon intravenous administration. Results showed that by finely tuning nanoprecipitation parameters, PLGA NPs coated with surfactants with a size around 150 nm could provide a sustained release of PTX for >2 weeks. Surface coatings could increase cellular uptake efficiency when compared with noncoated NPs, and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) showed the most significant enhancement. The in vivo evaluation of TPGS-PLGA NPs showed amplified accumulation (>800% after 96 h) of PTX in the brain tissue when compared with bare NPs and Taxol. Therefore, PLGA-NPs with PLGA-TPGS coating demonstrate a promising approach to efficiently transport PTX across blood-brain barrier in a safer manner, with the advantages of easy formulation, lower production cost, and higher encapsulation efficiency.
表面修饰的聚（丙交酯-共-乙交酯）PLGA 纳米粒子（NPs）通过纳米沉淀法制备，以获得脑肿瘤中紫杉醇（PTX）的治疗浓度。在体外评估了 NPs 在 C6 神经胶质瘤细胞上的细胞摄取和细胞毒性，并在静脉给药后使用 BALB/c 小鼠研究了脑穿透和生物分布。结果表明，通过精细调整纳米沉淀参数，可以制备出尺寸约为 150nm 的表面涂有表面活性剂的 PLGA NPs，其可以持续释放超过 2 周的 PTX。与未涂层的 NPs 相比，表面涂层可以提高细胞摄取效率，而 d-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS）的效果最为显著。体内评估 TPGS-PLGA NPs 显示，与裸 NPs 和 Taxol 相比，PTX 在脑组织中的积累增加了>800%（96 小时后）。因此，具有 PLGA-TPGS 涂层的 PLGA-NPs 提供了一种有前途的方法，可更有效地以更安全的方式将 PTX 跨血脑屏障运输，其具有易于配方、生产成本更低和更高的包封效率的优点。
