Size-Dependent Ability of Liposomes to Accumulate in the Ischemic Myocardium and Protect the Heart.
Size-Dependent Ability of Liposomes to Accumulate in the Ischemic Myocardium and Protect the Heart.
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DOI：
10.1097/fjc.0000000000000606
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发表时间：
2018-09
影响因子：
3
通讯作者：
Khaliulin I
中科院分区：
文献类型：
--
作者：
Mukhamadiyarov RA;Senokosova EA;Krutitsky SS;Voevoda DV;Pyshnaya IA;Ivanov VV;Lewis MJ;Khaliulin I
脂质体具有用于药物输送的潜力。同时，脂质体的大小可能影响它们在靶组织中的积累。我们研究了2种脂质体（直径约70 nm和110 nm）在缺血时的心肌蓄积及其对缺血/再灌注损伤的影响。用脂质体对离体大鼠心脏进行30分钟的低流量缺血，然后进行30分钟的无脂质体再灌注。用荧光染料尼罗红装载脂质体，以评估其在心肌中的积累情况。采用力-速度特性和冠状动脉血流（CF）评价再灌注时心功能恢复情况。乳酸脱氢酶释放评价再灌注损伤。此外，在正常灌注70 nm脂质体的心脏中，评估CF和收缩性。与大脂质体相比，小脂质体在心肌和线粒体中的积累量分别增加了6倍和4倍。重要的是，即使没有任何联合药物，两种脂质体也能改善功能恢复并减少乳酸脱氢酶的释放。然而，在再灌注过程中，较小的脂质体比较大的颗粒表现出更高的保护和血管扩张作用。这些脂质体也增加了正常灌注时的CF和收缩性。我们认为脂质体的保护作用可能与其膜稳定作用有关。
Liposomes have the potential to be used for drug delivery. Meanwhile, liposome size may affect their accumulation in the target tissue. We investigated the myocardial accumulation of 2 populations of liposomes (∼70 and 110 nm diameter) during ischemia and their effect on ischemia/reperfusion injury. Isolated rat hearts were subjected to 30 minutes of low-flow ischemia with the liposomes, followed by 30 minutes of liposome-free reperfusion. The liposomes were loaded with the fluorescent dye Nile Red to assess their accumulation in the myocardium. The cardiac functional recovery during reperfusion was evaluated using force–velocity characteristics and coronary flow (CF). Reperfusion injury was evaluated by lactate dehydrogenase release. In addition, CF and contractility were assessed in hearts perfused normally with 70 nm liposomes. There was a 6- and 4-fold greater accumulation of the small liposomes in the myocardium and mitochondria, respectively, compared with the large liposomes. Importantly, even without any incorporated drugs, both populations of liposomes improved functional recovery and reduced lactate dehydrogenase release. However, the smaller liposomes showed significantly higher protective and vasodilatory effects during reperfusion than the larger particles. These liposomes also increased CF and contractility during normal perfusion. We suggest that the protective properties of the liposomes could be related to their membrane-stabilizing effect.