Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery
Distribution of lipid-based nanoparticles to infarcted myocardium with potential application for MRI-monitored drug delivery
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DOI：
10.1016/j.jconrel.2012.06.035
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发表时间：
2012-09-10
影响因子：
10.8
通讯作者：
Strijkers, Gustav J.
中科院分区：
文献类型：
--
作者：
Paulis, Leonie E.;Geelen, Tessa;Strijkers, Gustav J.
心肌梗死后的不良心脏重构最终导致心力衰竭。为了刺激梗塞中的修复过程，需要治疗剂的有效递送和保留。本研究的目的是表征不同尺寸的长循环脂质纳米颗粒，即胶束（类似于15 nm）和脂质体（类似于100 nm），在心肌梗死（MI）小鼠模型中的分布模式。通过永久性闭塞左冠状动脉在小鼠（n = 38）中诱导MI。手术后一天和一周检查了静脉给药后的纳米颗粒积聚，分别代表MI的急性期和慢性期。采用胶束和脂质体中顺磁性脂质的体内磁共振成像来监测纳米颗粒向梗死心肌的运输。荧光脂质的离体高分辨率荧光显微镜被用来确定纳米颗粒在心肌中的确切位置，在急性和慢性MI中，胶束渗透到整个梗死区域，这使得它们非常适合用于心脏保护或抗重塑药物的局部递送。脂质体显示出更慢和更受限制的从脉管系统外渗，因此是用于递送促血管生成药物的有吸引力的载体。重要的是，用MRI非侵入性地可视化胶束和脂质体的能力为开发有效的心脏保护治疗干预创造了一种通用的方法。(C)2012年爱思唯尔B。V.保留所有权利。
Adverse cardiac remodeling after myocardial infarction ultimately causes heart failure. To stimulate reparative processes in the infarct, efficient delivery and retention of therapeutic agents is desired. This might be achieved by encapsulation of drugs in nanoparticles.The goal of this study was to characterize the distribution pattern of differently sized long-circulating lipid-based nanoparticles, namely micelles (similar to 15 nm) and liposomes (similar to 100 nm), in a mouse model of myocardial infarction (MI). MI was induced in mice (n = 38) by permanent occlusion of the left coronary artery. Nanoparticle accumulation following intravenous administration was examined one day and one week after surgery, representing the acute and chronic phase of MI, respectively. In vivo magnetic resonance imaging of paramagnetic lipids in the micelles and liposomes was employed to monitor the trafficking of nanoparticles to the infarcted myocardium. Ex vivo high-resolution fluorescence microscopy of fluorescent lipids was used to determine the exact location of the nanoparticles in the myocardium.In both acute and chronic MI, micelles permeated the entire infarct area, which renders them very suited for the local delivery of cardioprotective or anti-remodeling drugs. Liposomes displayed slower and more restricted extravasation from the vasculature and are therefore an attractive vehicle for the delivery of pro-angiogenic drugs. Importantly, the ability to non-invasively visualize both micelles and liposomes with MRI creates a versatile approach for the development of effective cardioprotective therapeutic interventions. (C) 2012 Elsevier B. V. All rights reserved.