Enhanced treatment for cerebral ischemia-reperfusion injury of puerarin loading liposomes through neutrophils-mediated targeted delivery

Abstract

The recovery of blood circulation following cerebral infarction-associated thrombolysis brings new damage to the brain, which is cerebral ischemia-reperfusion injury (CIRI). Inflammation is the main pathological mechanism of CIRI. The inflammatory response triggered by cerebral ischemia-reperfusion provides neutrophils with a special opportunity to facilitate drug delivery to the site of ischemic penumbra through the chemotaxis of inflammatory factors by neutrophils. Puerarin is an isoflavone derivative with a significant neuroprotective effect in vitro. But the blood-brain barrier (BBB) impedes its therapeutic efficacy on CIRI within the brain. Inspired by the pathological process, we have used neutrophils as carriers to enhance the BBB penetration of liposomes loaded with puerarin and improve the concentration of puerarin in the brain parenchyma in this study. These results showed that puerarin-containing liposomes were released in response to inflammatory conditions associated with brain injury to enhance the neuroprotection effect at the ischemic penumbra.