Departmentof Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009 Sep-Oct;1(5):530-9. doi: 10.1002/wnan.46.
A major obstacle to drug therapy for treatment of potential myocardial infarction is the limited access to the ischemic myocardium by drugs in an active form. Encouraging results have been reported with liposomes loaded with ATP in a variety of in vitro and in vivo models. We describe methods for optimized encapsulation of ATP in liposomes, enhancement of their effectiveness by increasing circulation time, and targeting of injured myocardial cells with surface attached antimyosin. In isolated ischemic rat hearts, ATP-loaded liposomes and ATP-loaded immunoliposomes effectively protected myocardium from ischemia/reperfusion damage as measured by systolic and diastolic functional improvements. In vivo, in rabbits with induced localized myocardial ischemia, liposomal encapsulation of ATP significantly diminished the proportion of ventricular muscle at risk that was irreversibly damaged during reperfusion. Therefore, ATP encapsulated in liposomes can provide an effective exogenous source for in vivo application which can protect ischemically damaged hearts.
药物治疗潜在心肌梗死的主要障碍是药物以活性形式进入缺血心肌的途径有限。脂质体负载 ATP 在各种体外和体内模型中已经取得了令人鼓舞的结果。我们描述了优化 ATP 包封在脂质体中的方法，通过增加循环时间来提高其效力，并通过表面附着的抗肌球蛋白靶向损伤的心肌细胞。在分离的缺血大鼠心脏中，负载 ATP 的脂质体和负载 ATP 的免疫脂质体通过改善收缩和舒张功能有效地保护心肌免受缺血/再灌注损伤。在体内，用诱导的局部心肌缺血的兔中，ATP 包封在脂质体中可显著减少再灌注期间不可逆损伤的心室肌的风险比例。因此，脂质体包封的 ATP 可为体内应用提供有效的外源来源，从而保护缺血性损伤的心脏。
