Enhanced brain delivery of hypoxia-sensitive liposomes by hydroxyurea for rescue therapy of hyperacute ischemic stroke
Kai Wang, Wentao Zhou, Xiangyu Jin, Xuwei Shang, Xiaomei Wu, Lijuan Wen, Sufen Li, Yiling Hong, Jia Ke, Yichong Xu, Hong Yuan, Fuqiang Hu
Abstract
model. HYD also increased the BBB permeability and promoted microcirculation in the hyperacute phase of stroke. The neutrophil-like cell-membrane-fusogenic hypoxia-sensitive liposomes exhibited excellent performance in targeting the inflamed brain microvascular endothelial cells, enhancing cell association, and promoting rapid hypoxic-responsive release in the hypoxic microenvironment. Overall, the combined HYD and hypoxia-sensitive liposome dosing regimen effectively decreased the cerebral infarction volume and relieved neurological dysfunction in rats that had ischemic strokes; these therapies were involved in the anti-oxidative stress effect and the neurotrophic effect mediated by macrophage migration inhibitory factor.