Levchenko Tatyana S, Hartner William C, Verma Daya D, Bernstein Eugene A, Torchilin Vladimir P
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA.
Methods Mol Biol. 2010;605:361-75. doi: 10.1007/978-1-60327-360-2_25.
ATP cannot be effectively delivered to most tissues including the ischemic myocardium without protection from degradation by plasma endonucleotidases. However, it has been established that ATP can be delivered to various tissues by its encapsulation within liposomal preparations. We describe here, the materials needed and methods used to optimize the encapsulation of ATP in liposomes, enhance their effectiveness by increasing their circulation time and target injured myocardial cells with liposomal surface anti-myosin antibody. Additionally, we outline methods for ex vivo studies of these ATP liposomal preparations in an isolated ischemic rat heart model and for in vivo studies of rabbits with an induced myocardial infarction. The expectation is that these methods will provide a basis for continued studies of effective ways to deliver energy substrates to the ischemic myocardium.
在没有免受血浆核酸内切酶降解保护的情况下，ATP无法有效地输送到包括缺血心肌在内的大多数组织。然而，已经证实，通过将ATP包裹在脂质体制剂中，可以将其输送到各种组织。我们在此描述优化ATP脂质体包封所需的材料和方法，通过延长其循环时间来提高其有效性，并利用脂质体表面抗肌球蛋白抗体靶向损伤的心肌细胞。此外，我们概述了在离体缺血大鼠心脏模型中对这些ATP脂质体制剂进行体外研究以及对诱导心肌梗死的兔子进行体内研究的方法。预期这些方法将为继续研究向缺血心肌输送能量底物的有效途径提供基础。
