School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong Special Administrative Region.
Department of Pharmacology and Pharmacy, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
Int J Pharm. 2021 Apr 1;598:120224. doi: 10.1016/j.ijpharm.2021.120224. Epub 2021 Jan 22.
Ibuprofen (IBP), a common non-steroidal anti-inflammatory drug (NSAID) with a log P of 3.51, has been shown to possess potential benefit in the treatment of Alzheimer's disease. However, the bioavailability of IBP to the brain is poor, which can be linked to its extensive binding to plasma proteins in the blood. This study aimed to evaluate the nanoparticle production of IBP by flash nanoprecipitation (FNP) technology, and to determine whether the nanoparticles prepared by FNP could enhance the delivery of IBP into the brain. Polymeric IBP nanoparticles were prepared with poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) diblock copolymer as stabilizer under optimized conditions using a four-stream multi-inlet vortex mixer (MIVM). The optimized nanoparticles displayed a mean particle size of around 50 nm, polydispersity index of around 0.2, drug loading of up to 30% and physical stability of up to 34 days. In-depth surface characterization using zeta potential measurement, atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) showed that the surfaces of these nanoparticles were covered with the hydrophilic PEG groups from the diblock copolymer. In vivo brain uptake study of the IBP nanoparticles indicated that the particles, when coated with polysorbate 80, displayed an enhanced brain uptake. However, the extent of brain uptake enhancement appeared limited, possibly due to a rapid release of IBP from the nanoparticles into the blood stream following intravenous administration.
布洛芬（IBP）是一种常见的非甾体抗炎药（NSAID），其分配系数（log P）为 3.51，已被证明在治疗阿尔茨海默病方面具有潜在益处。然而，IBP 向大脑的生物利用度较差，这可能与其在血液中与血浆蛋白广泛结合有关。本研究旨在评估通过闪式纳米沉淀（FNP）技术生产 IBP 的纳米粒子，并确定通过 FNP 制备的纳米粒子是否可以增强 IBP 向大脑的递送。在优化条件下，使用四流多入口旋流混合器（MIVM），以聚乙二醇-聚乳酸（PEG-PLA）两亲性嵌段共聚物作为稳定剂，制备了 IBP 纳米粒子。优化后的纳米粒子的平均粒径约为 50nm，多分散指数约为 0.2，载药量高达 30%，物理稳定性长达 34 天。使用 zeta 电位测量、原子力显微镜（AFM）和 X 射线光电子能谱（XPS）进行深入的表面特性分析表明，这些纳米粒子的表面覆盖有两亲性嵌段共聚物的亲水性 PEG 基团。IBP 纳米粒子的体内脑摄取研究表明，当用聚山梨酯 80 包被时，这些粒子显示出增强的脑摄取。然而，脑摄取增强的程度似乎有限，可能是由于静脉注射后纳米粒子中的 IBP 迅速释放到血流中所致。
