Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA; Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Benha University, Qalyubia, Egypt.
Nanomedicine. 2020 Oct;29:102246. doi: 10.1016/j.nano.2020.102246. Epub 2020 Jun 24.
Globally, ischemic stroke is a leading cause of death and adult disability. Previous efforts to repair damaged brain tissue following ischemic events have been hindered by the relative isolation of the central nervous system. We have developed a gelatin nanoparticle-mediated intranasal drug delivery system as an efficient, non-invasive method for delivering 17β-estradiol (E2) specifically to the brain, enhancing neuroprotection, and limiting systemic side effects. Young adult male C57BL/6 J mice subjected to 30 min of middle cerebral artery occlusion (MCAO) were administered intranasal preparations of E2-GNPs, water soluble E2, or saline as control 1 h after reperfusion. Following intranasal administration of 500 ng E2-GNPs, brain E2 content rose by 5.24 fold (P<0.0001) after 30 min and remained elevated by 2.5 fold at 2 h (P<0.05). The 100 ng dose of E2-GNPs reduced mean infarct volume by 54.3% (P<0.05, n=4) in comparison to saline treated controls, demonstrating our intranasal delivery system's efficacy.
在全球范围内，缺血性中风是导致死亡和成年残疾的主要原因。以前，人们试图在缺血性事件后修复受损的脑组织，但由于中枢神经系统相对隔离，这些努力受到了阻碍。我们开发了一种明胶纳米颗粒介导的经鼻药物传递系统，作为一种将 17β-雌二醇（E2）特异性递送至大脑、增强神经保护和限制全身副作用的有效、非侵入性方法。30 分钟大脑中动脉闭塞（MCAO）后，将 E2-GNP、水溶性 E2 或盐水（作为对照）鼻内制剂给予成年雄性 C57BL/6 J 小鼠，再灌注后 1 小时给予。经鼻给予 500 ng E2-GNP 后，脑内 E2 含量在 30 分钟内增加了 5.24 倍（P<0.0001），2 小时时仍升高 2.5 倍（P<0.05）。与盐水处理的对照组相比，E2-GNP 的 100ng 剂量可使平均梗死体积减少 54.3%（P<0.05，n=4），证明了我们的经鼻给药系统的疗效。
