Title:Nasal Delivery of Antioxidants by Cholesterol-incorporated Liposomes Extends the Neuroprotective Time Window in Cerebral Ischemia
Volume: 23
Issue: 40
Author(s): Seul Ki Min, Yeo Seon Kwon, Myung Kwon Cho and Hwa Sung Shin*
Affiliation:
- Department of Biological Engineering, Inha University, Incheon, 22212,Korea
Keywords:
Ischemia-reperfusion, Time window, Nasal administration, Liposome, Cholesterol, C-Phycocyanin.
Abstract: Antioxidants have the potential to prevent cerebral ischemia-reperfusion (IR)-associated secondary
damage induced by reactive oxygen species (ROS); however, the short therapeutic time window of IR is a considerable
obstacle. Nano-sized nasal delivery systems provide an effective means of delivering drugs through the
BBB, but few such systems have been developed to extend the treatment time window in IR. In this work, a nanosized
nasal delivery system for antioxidants was found to have the potential to extend the neuroprotective time
window. The authors chose to use the antioxidant C-phycocyanin (C-Pc) to design a neuroprotective liposome
with a long life, controllable release, and high neuronal uptake rate. Liposomes formulated with various cholesterol
to phospholipid ratios were assessed thermodynamically, kinetically, and biologically. Thermodynamically
stable, monodispersive, and release-controllable C-Pc liposomes were more effectively taken up by Neuro2a cells
than free C-Pc and were biocompatible, maintaining the anti-oxidative properties of C-Pc. When optimal C-Pc
liposomes were administered to middle cerebral artery occlusion (MCAO) rats 2 h after onset, infarct sizes were
smaller and behavioral activities improved compared with the same metrics in free C-Pc-treated rats. Liposomal
delivery still reduced infarct sizes and improved behavioral activity 6 h after onset, whereas free C-Pc did not.
