Department of Medicine 1, University Hospital Frankfurt, Frankfurt, Germany; Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary; Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, Veszprém, Hungary.
Department of Medicine 1, University Hospital Frankfurt, Frankfurt, Germany.
J Control Release. 2019 Jan 10;293:63-72. doi: 10.1016/j.jconrel.2018.11.017. Epub 2018 Nov 17.
For many years, delivering drug molecules across the blood brain barrier has been a major challenge. The neuropeptide nerve growth factor is involved in the regulation of growth and differentiation of cholinergic neurons and holds great potential in the treatment of stroke. However, as with many other compounds, the biomolecule is not able to enter the central nervous system. In the present study, nerve growth factor and ultra-small particles of iron oxide were co-encapsulated into a chemically crosslinked albumin nanocarrier matrix which was modified on the surface with apolipoprotein E. These biodegradable nanoparticles with a size of 212 ± 1 nm exhibited monodisperse size distribution and low toxicity. They delivered NGF through an artificial blood brain barrier and were able to induce neurite outgrowth in PC12 cells in vitro. In an animal model of stroke, the infarct size was significantly reduced compared to the vehicle control. The combination therapy of NGF and the small-molecular MEK inhibitor U0126 showed a slight but not significant difference compared to U0126 alone. However, further in vivo evidence suggests that successful delivery of the neuropeptide is possible as well as the synergism between those two treatments.
多年来，将药物分子递送到血脑屏障一直是一个主要挑战。神经肽神经生长因子参与胆碱能神经元的生长和分化的调节，在中风治疗中有很大的潜力。然而，与许多其他化合物一样，这种生物分子无法进入中枢神经系统。在本研究中，神经生长因子和超小氧化铁颗粒被共同包封在一种化学交联的白蛋白纳米载体基质中，该基质在表面用载脂蛋白 E 进行修饰。这些具有 212±1nm 尺寸的生物可降解纳米颗粒表现出单分散的尺寸分布和低毒性。它们通过人工血脑屏障传递 NGF，并能够在体外诱导 PC12 细胞的突起生长。在中风动物模型中，与载体对照组相比，梗塞面积显著减小。与单独使用 U0126 相比，NGF 和小分子 MEK 抑制剂 U0126 的联合治疗仅显示出轻微但无统计学意义的差异。然而，进一步的体内证据表明，神经肽的成功传递以及这两种治疗方法之间的协同作用是可能的。
