cRGD mediated liposomes enhanced antidepressant-like effects of edaravone in rats
cRGD mediated liposomes enhanced antidepressant-like effects of edaravone in rats
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cRGD介导的脂质体增强依达拉奉在大鼠中的抗抑郁样作用
DOI：
10.1016/j.ejps.2014.03.006
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发表时间：
2014-07-16
影响因子：
4.6
通讯作者：
Lu, Lin
中科院分区：
文献类型：
--
作者：
Qin, Jing;Zhang, Ruo-Xi;Lu, Lin
治疗结果的延迟发作是目前抗抑郁药的一个主要缺点。血脑屏障是阻碍药物进入大脑的最重要的瓶颈。因此，开发具有快速起效和持续作用的新型抗抑郁药物迫在眉睫。RGD脂质体具有良好的脑靶向给药效果，提高了药物进入脑的速率。在本研究中，我们制备了装载依达拉奉的环状RGD脂质体（cRGD-ERLs），并在大鼠身上评估了这种药物传递系统的潜在抗抑郁样作用。结果显示，单次注射cRGD-ERLs在强迫游泳和新奇抑制喂养试验中均具有显著的抗抑郁样作用。此外，急性cRGD-ERLs增加了内侧前额叶皮层c-fos的表达，表明cRGD-ERLs可以激活神经元功能。此外，cRGD-ERLs逆转了脂多糖（LPS）诱导的血浆细胞因子IL-1 β和IL-6的升高，提示细胞因子水平的正常化可能参与了cRGD-ERLs的行为反应。最后，在强迫游泳试验中，cRGD-ERLs可以阻止LPS诱导的不动性增加。总的来说，目前的数据揭示了一种新的脑靶向药物传递系统，可以通过增加到大脑的穿越率来改善抗抑郁药物的治疗效果。(C) 2014 Elsevier B.V.版权所有
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-1 beta 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. (C) 2014 Elsevier B.V. All rights reserved.