脂质体
体内
外渗
药物输送
心肌梗塞
离体
分布(数学)
药理学
磁共振成像
瑞舒伐他汀
医学
毒品携带者
胶束
生物医学工程
埃文斯蓝
药品
化学
心脏病学
病理
内科学
放射科
生物化学
生物
数学分析
生物技术
数学
有机化学
物理化学
水溶液
作者
Leonie E. M. Paulis,Tessa Geelen,Michael Kuhlmann,Bram F. Coolen,Michael Schäfers,Klaas Nicolay,Gustav J. Strijkers
标识
DOI:10.1016/j.jconrel.2012.06.035
摘要
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 (~ 15 nm) and liposomes (~ 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.
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