Abstract

Novel therapeutics for the treatment of ischemic stroke remains to be the unmet clinical needs. Previous studies have indicated that salvianolic acid A (SAA) is a promising candidate for the treatment of the brain diseases. However, SAA has poor absolute bioavailability and does not efficiently cross the intact blood-brain barrier (BBB), which limit its efficacy. To this end we developed a brain-targeted liposomes for transporting SAA via the BBB by incorporating the liposomes to a transport receptor, insulin-like growth factor-1 receptor (IGF1R). The liposomes were prepared by ammonium sulfate gradients loading method. The prepared SAA-loaded liposomes (Lipo/SAA) were modified with IGF1R monoclonal antibody to generate IGF1R antibody-conjugated Lipo/SAA (IGF1R-targeted Lipo/SAA). The penetration of IGF1R-targeted Lipo/SAA into the brain was confirmed by labeling with Texas Red, and their efficacy were evaluate using middle cerebral artery occlusion (MCAO) model. The results showed that IGF1R-targeted Lipo/SAA are capable of transporting SAA across the BBB into the brain, accumulation in brain tissue, and sustained releasing SAA for several hours. Administration o IGF1R-targeted Lipo/SAA notably reduced infarct size and neuronal damage, improved neurological function and inhibited cerebral inflammation, which had much higher efficiency than no-targeted SAA.

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