Department of Bioengineering, University of Illinois, Urbana, IL, 61801, USA.
Drug Deliv Transl Res. 2014 Dec;4(5-6):395-9. doi: 10.1007/s13346-014-0208-9.
As a leading cause of death and adult disability, ischemic stroke requires the development of non-invasive, long-acting treatments. Osteopontin (OPN) is an endogenous protein shown to have neuroprotective effects in the post-ischemic brain of rats when administered through the non-invasive, intranasal pathway. Previously, gelatin microspheres (GMSs) have been shown to enhance the neuroprotective effects of OPN when used as a carrier during instrastriatal administration, but GMSs are generally too large to enter the brain parenchyma following intranasal administration. Here, gelatin nanoparticles (GNPs) were investigated as a carrier for intranasal delivery of an OPN peptide for the treatment of ischemic stroke. We not only successfully fabricated GNPs with a uniform shape, but also demonstrated the ability of these GNPs to pass into the brain parenchyma following intranasal administration. Critically, the use of GNPs as a carrier allowed for a 71.57 % reduction in mean infarct volume and extended the therapeutic window of intranasally administered OPN peptide to at least 6 h post-middle cerebral artery occlusion (MCAO). Our findings support the development of GNPs as a promising drug delivery platform for the intranasal treatment of ischemic stroke and, potentially, other neurologic disorders.
作为导致死亡和成年人残疾的主要原因之一，缺血性中风需要开发非侵入性、长效的治疗方法。骨桥蛋白（OPN）是一种内源性蛋白质，当通过非侵入性的鼻内途径给药时，已被证明在大鼠缺血后脑中具有神经保护作用。先前，明胶微球（GMS）已被证明在作为载体用于纹状体给药时可增强 OPN 的神经保护作用，但 GMS 通常太大而无法在鼻内给药后进入脑实质。在这里，明胶纳米粒（GNPs）被研究作为一种载体，用于经鼻内递送至缺血性中风治疗的 OPN 肽。我们不仅成功地制备了具有均匀形状的 GNPs，还证明了这些 GNPs 能够在经鼻内给药后进入脑实质。至关重要的是，使用 GNPs 作为载体可以使平均梗死体积减少 71.57%，并将经鼻内给予的 OPN 肽的治疗窗口延长至至少 6 小时的大脑中动脉闭塞（MCAO）后。我们的发现支持将 GNPs 开发为用于缺血性中风和潜在其他神经疾病的经鼻治疗的有前途的药物递送平台。
