Multidrug-loaded liposomes prevent ischemic stroke through intranasal administration
Shuang Yu, Dan Li, Ai Shi, Yu Long, Jie Deng, Yin Ma, Xiaoqiu Li, Jing Wen, Yue Hu, Xiao‐Fang He, Yuanyuan Wu, Nan Li, Mengnan Zhao
Abstract
Baicalin (BA), a multi-target neuroprotective agent, has poor solubility resulting in low bioavailability. In this study, multidrug-loaded liposomes were prepared by encapsulating BA, borneol (BO) and cholic acid (CA) to prevent ischemic stroke. BBC-LP were administered intranasally (i.n.) to deliver into the brain for neuroprotection. Finally, potential mechanism of BBC treating ischemic stroke (IS) was explored by network pharmacology. In this study, BBC-LP was prepared by reverse evaporation method, and the encapsulation efficiency (EE) of the optimized liposomes was 42.69% and the drug loading (DL) was 6.17%. The liposomes had low mean particle size (156.62 ± 2.96 nm), polydispersity index (PDI) (0.195) and zeta potential (-0.99 mv). Compared to BBC, pharmacodynamic studies revealed that BBC-LP significantly improved neurological deficits, brain infarct volume, and cerebral pathology in MCAO rats. Toxicity studies showed that BBC-LP was not irritating to the nasal mucosa. These results suggest that BBC-LP can safely and effectively ameliorate IS injury by i.n. administration. Moreover, it's neuroprotective function may be related to the anti-apoptotic and anti-inflammatory effects exerted by phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway.