cRGD mediated liposomes enhanced antidepressant-like effects of edaravone in rats

The delayed onset of therapeutic outcomes is a major drawback of the current antidepressants. The blood–brain barrier is the most important bottleneck impeding drug transport into the brain. Therefore, development of novel antidepressant medications with rapid onset and sustained activity is urgent. RGD liposomes showed an excellent effect of brain-targeting drug delivery and increased the entering rate to the brain. In the present study, we prepared cyclic RGD liposomes loaded with edaravone (cRGD-ERLs) and evaluated the potential antidepressant-like effects of this drug delivery system in rats. The results showed single injection of cRGD-ERLs produced significant antidepressant-like effects in both forced swim and novelty suppressed feeding test. Moreover, acute cRGD-ERLs increased the expression of c-fos in the medial prefrontal cortex, suggesting that cRGD-ERLs could activate the neuronal function. Furthermore, cRGD-ERLs reversed the increase of lipopolysaccharides (LPS)-induced plasma cytokine IL-1β and IL-6, suggesting that normalization of cytokine level might be involved in the behavioral response of cRGD-ERLs. Finally, cRGD-ERLs prevented the increase of immobility induced by LPS in the forced swim test. Overall, the current data revealed a novel brain-target drug delivery system, which can be used to improve the therapeutic outcomes of antidepressants by increase of crossing rate to the brain.

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