Faculty of Engineering, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
Bar-Ilan Institute of Nanotechnologies and Advanced Materials, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
Small. 2019 Nov;15(45):e1904203. doi: 10.1002/smll.201904203. Epub 2019 Sep 4.
Nerve growth factor (NGF) plays a vital role in reducing the loss of cholinergic neurons in Alzheimer's disease (AD). However, its delivery to the brain remains a challenge. Herein, NGF is loaded into degradable oxidized porous silicon (PSiO ) carriers, which are designed to carry and continuously release the protein over a 1 month period. The released NGF exhibits a substantial neuroprotective effect in differentiated rat pheochromocytoma PC12 cells against amyloid-beta (Aβ)-induced cytotoxicity, which is associated with Alzheimer's disease. Next, two potential localized administration routes of the porous carriers into murine brain are investigated: implantation of PSiO chips above the dura mater, and biolistic bombardment of PSiO microparticles through an opening in the skull using a pneumatic gene gun. The PSiO -implanted mice are monitored for a period of 8 weeks and no inflammation or adverse effects are observed. Subsequently, a successful biolistic delivery of these highly porous microparticles into a live-mouse brain is demonstrated for the first time. The bombarded microparticles are observed to penetrate the brain and reach a depth of 150 µm. These results pave the way for using degradable PSiO carriers as potential localized delivery systems for NGF to the brain.
神经生长因子（NGF）在减少阿尔茨海默病（AD）中胆碱能神经元的损失方面起着至关重要的作用。然而，将其递送到大脑仍然是一个挑战。在此，NGF 被装载到可降解的氧化多孔硅（PSiO）载体中，这些载体旨在携带并在 1 个月的时间内持续释放蛋白质。释放的 NGF 在分化的大鼠嗜铬细胞瘤 PC12 细胞中对淀粉样β（Aβ）诱导的细胞毒性表现出显著的神经保护作用，这与阿尔茨海默病有关。接下来，研究了两种潜在的多孔载体在小鼠脑内的局部给药途径：将 PSiO 芯片植入硬脑膜上方，以及使用气动基因枪通过颅骨上的开口对 PSiO 微球进行弹道轰击。监测 PSiO 植入的小鼠 8 周，未观察到炎症或不良反应。随后，首次成功地将这些高度多孔的微球生物递送到活体小鼠的大脑中。轰击的微球被观察到穿透大脑并达到 150 µm 的深度。这些结果为使用可降解 PSiO 载体作为 NGF 向大脑的潜在局部递药系统铺平了道路。
