Sustained release of VEGF through PLGA microparticles improves vasculogenesis and tissue remodeling in an acute myocardial ischemia-reperfusion model
Sustained release of VEGF through PLGA microparticles improves vasculogenesis and tissue remodeling in an acute myocardial ischemia-reperfusion model
复制标题
DOI：
10.1016/j.jconrel.2010.07.097
复制
发表时间：
2010-10-01
影响因子：
10.8
通讯作者：
Blanco-Prieto, Maria J.
中科院分区：
文献类型：
--
作者：
Formiga, Fabio R.;Pelacho, Beatriz;Blanco-Prieto, Maria J.
在局部缺血模型中使用促血管生成生长因子与临床环境中有限的成功相关，部分原因是由于注射的细胞因子的短暂作用。微粒系统的使用可以允许局部和持续的细胞因子释放，从而延长生物效应，诱导组织血管再生。为了评估VEGF（165）作为连续释放给药在缺血性疾病中的潜力，我们在大鼠缺血-再灌注模型中比较了负载VEGF（165）的聚（乳酸-共-乙醇酸）（PLGA）微粒（MP）与游离VEGF或对照空微粒的递送效果。在移植后一个多月，可以在梗塞动物的心肌中检测到负载VEGF 165的微粒，并在体外和体内提供活性蛋白的持续递送。治疗后一个月，在用VEGF微粒治疗的动物中观察到血管生成（小口径小窝蛋白-1阳性血管）和动脉生成（α-SMA阳性血管）的增加（p < 0.05），但在空微粒或无VEGF组中没有观察到。与该数据相关，在VEGF-微粒组中也检测到心脏的正性重塑，具有显著更大的LV壁厚度（p < 0.01）。结论：PICA微粒是一种可行的、有前景的细胞因子载体系统，可用于治疗心肌缺血。这种策略可以在临床前和临床研究中扩大和探索。(C)2010爱思唯尔有限公司版权所有。
The use of pro-angiogenic growth factors in ischemia models has been associated with limited success in the clinical setting, in part owing to the short lived effect of the injected cytokine. The use of a microparticle system could allow localized and sustained cytokine release and consequently a prolonged biological effect with induction of tissue revascularization. To assess the potential of VEGF(165) administered as continuous release in ischemic disease, we compared the effect of delivery of poly(lactic-co-glycolic acid) (PLGA) microparticles (MP) loaded with VEGF(165) with free-VEGF or control empty microparticles in a rat model of ischemia-reperfusion. VEGF165 loaded microparticles could be detected in the myocardium of the infarcted animals for more than a month after transplant and provided sustained delivery of active protein in vitro and in vivo. One month after treatment, an increase in angiogenesis (small caliber caveolin-1 positive vessels) and arteriogenesis (alpha-SMA-positive vessels) was observed in animals treated with VEGF microparticles (p < 0.05), but not in the empty microparticles or free-VEGF groups. Correlating with this data, a positive remodeling of the heart was also detected in the VEGF-microparticle group with a significantly greater LV wall thickness (p < 0.01). In conclusion, PICA microparticle is a feasible and promising cytokine delivery system for treatment of myocardial ischemia. This strategy could be scaled up and explored in pre-clinical and clinical studies. (C) 2010 Elsevier B.V. All rights reserved.