Nanoemulsions of Hydroxysafflor Yellow A for Enhanced Brain Delivery in Cerebral Ischemia Reperfusion-injured mice: Physicochemical and In Vivo Performances

Abstract

Stroke has always been a disease threatening human life and health worldwide. Here, we synthesized a new type of hyaluronic acid-modified multi-walled carbon nanotube. Then we prepared hydroxysafflor yellow A-hydroxypropyl-β-cyclodextrin phospholipid complex water-in-oil nanoemulsion with hyaluronic acid-modified multi-walled carbon nanotubes and chitosan (HC@HMC) for oral treatment of ischemic stroke. First, we measured the intestinal absorption and pharmacokinetics of HC@HMC in rats. We found that the intestinal absorption and the pharmacokinetic behavior of HC@HMC is better than HYA. Then we detected intracerebral concentrations after oral administration of HC@HMC and found that more HYA crossed the blood-brain barrier (BBB). Finally, we evaluated the efficacy of HC@HMC in middle cerebral artery occlusion/reperfusion (MCAO/R)-treated mice. In MCAO/R mice, oral administration of HC@HMC demonstrated a significant protection against cerebral ischemia-reperfusion injury (CIRI). And we also found HC@HMC may exert a protective effect on cerebral ischemia-reperfusion injury through COX2/PGD2/DPs pathway. These results suggest that oral administration of HC@HMC may be a new strategy for the treatment of stroke.