Brain targeted borneol-baicalin liposome improves blood-brain barrier integrity after cerebral ischemia-reperfusion injury via inhibiting HIF-1α/VEGF/eNOS/NO signal pathway
Yu Long, Songyu Liu, Jinyan Wan, Yulu Zhang, Dan Li, Shuang Yu, Ai Shi, Nan Li, Fei He
Abstract
Baicalin (BA) is widely used in the treatment of cerebral ischemia-reperfusion injury (CIRI). The key to treating encephalopathy is to increase the amounts of drugs entering the brain. Borneol-baicalin liposome (BO-BA-LP) was prepared in previous research based on the characteristics of borneol (BO) in promoting drug brain entry. In this study, the effect of BO-BA-LP on improving blood-brain barrier (BBB) integrity was researched. Results showed BO-BA-LP may increase ability of BA to penetrate the cell membrane in vitro. Pharmacokinetic results showed the BO-BA-LP could increase concentrations of BA in plasma and brain tissues of normal and CIRI mice. Pharmacological results revealed BO-BA-LP could improve the neurological function, brain edema, and histopathology of CIRI mice. Besides, BO-BA-LP could protect BBB by regulating hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. The research showed that BO in BO-BA-LP could increase the absorption of BA by increasing BBB permeability, leading to a better therapeutic effect of BO-BA-LP on CIRI mice.