Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction.
Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction.
复制标题
纳米制剂利拉鲁肽的时空递送用于心肌梗死后的心脏再生
DOI：
10.2147/ijn.s132064
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发表时间：
2017
影响因子：
8
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
Qi Q;Lu L;Li H;Yuan Z;Chen G;Lin M;Ruan Z;Ye X;Xiao Z;Zhao Q
局部心肌内注射蛋白质到梗死心脏是心肌梗死（MI）后启动心脏再生的一个有吸引力的选择。利拉鲁肽是作为2型糖尿病的治疗药物而开发的，它被认为是心脏再生中最有前途的蛋白质候选物之一。这种蛋白质的治疗用途的一个重大挑战是其体内半衰期短。在本研究中，我们评价了载于聚（乳酸-羟基乙酸）-聚（乙二醇）（PLGA-PEG）纳米粒（NP-利拉鲁肽）中的利拉鲁肽对实验性MI的治疗作用和长期保留。已证明PLGA-PEG纳米颗粒（NP）可有效负载利拉鲁肽并以持续方式释放生物活性利拉鲁肽。对于体外试验，释放的利拉鲁肽保留了生物活性，通过其激活利拉鲁肽信号传导途径的能力进行测量。接下来，我们比较了心肌内注射生理盐水、空NP、游离利拉鲁肽和NP-利拉鲁肽在MI大鼠模型中的作用。在心肌中检测到NPs长达4周。更重要的是，心肌内注射NP-利拉鲁肽足以改善心功能（P<0.05），缩小梗死面积（P<0.05），保持壁厚（P <0.05），促进血管生成（P<0.05），并在注射后4周防止心肌细胞凋亡（P<0.05），而不影响血糖水平。NP-利拉鲁肽的局部、受控、心肌内给药代表了治疗MI的有效且有前景的策略。
The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function (P<0.05), attenuate the infarct size (P<0.05), preserve wall thickness (P<0.05), promote angiogenesis (P<0.05) and prevent cardiomyocyte apoptosis (P<0.05) at 4 weeks after injection without affecting glucose levels. The local, controlled, intramyocardial delivery of NP-liraglutide represents an effective and promising strategy for the treatment of MI.