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Nano encapsulated novel compound SA-10 with therapeutic activity in both acute and chronic murine hindlimb ischemia models
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 5.4 ) Pub Date : 2021-04-15 , DOI: 10.1016/j.nano.2021.102400
Louis Hinkle 1 , Duong Le 2 , Tam Nguyen 2 , Vy Tran 2 , Charles E Amankwa 3 , Courtney Weston 3 , Haifa Shen 1 , Kytai T Nguyen 2 , Maham Rahimi 4 , Suchismita Acharya 5
Affiliation  

The production dysregulation of reactive oxygen species (ROS) and nitric oxide (NO) in ischemic tissues results in endothelial dysfunction, hyperinflammation and poor blood circulation. Here, we report a hybrid molecule, SA-10 with both NO donating and ROS scavenging abilities that demonstrated potent cytoprotection and tube formation activity in endothelial cells under H2O2-induced oxidative stress. SA-10 loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (SA-10 NPs) were delivered intramuscularly (IM) to two murine hindlimb ischemia models. In the acute mode ischemia/reperfusion (I/R), the muscle damage, hyperinflammation, and lung edema were significantly reduced 3 days post-dose while in the chronic ischemia model, significant improvement of blood perfusion and physical endurance was observed over 30 days (P < 0.05). Elderly patients with acute and chronic limb ischemia have limited options for surgical or endovascular interventions, so we anticipate that a product like SA-10 NPs has potential as one of the therapeutic alternatives to surgery.



中文翻译:

在急性和慢性小鼠后肢缺血模型中具有治疗活性的纳米封装新型化合物 SA-10

缺血组织中活性氧 (ROS) 和一氧化氮 (NO) 的产生失调导致内皮功能障碍、过度炎症和血液循环不良。在这里,我们报告了一种混合分子SA-10 ,它同时具有 NO 供体和 ROS 清除能力,在 H 2 O 2诱导的氧化应激下,它在内皮细胞中表现出有效的细胞保护和管形成活性。负载SA-10 的聚乳酸-乙醇酸共聚物 (PLGA) 纳米颗粒 ( SA-10 NPs) 肌肉内 (IM) 递送至两个小鼠后肢缺血模型。在急性模式缺血/再灌注 (I/R) 中,肌肉损伤、过度炎症和肺水肿在给药后 3 天显着减少,而在慢性缺血模型中,在 30 天内观察到血液灌注和身体耐力的显着改善( P  < 0.05)。患有急性和慢性肢体缺血的老年患者对手术或血管内干预的选择有限,因此我们预计像SA-10 NPs这样的产品有可能成为手术的治疗替代品之一。

更新日期:2021-05-15
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