Nano encapsulated novel compound SA-10 with therapeutic activity in both acute and chronic murine hindlimb ischemia models

Louis Hinkle, Duong Le, Tam Nguyen, Vy Tran, Charles E. Amankwa, Courtney Weston, Haifa Shen, Kytai T. Nguyen, Maham Rahimi, Suchismita Acharya

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number102400
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume35
DOIs
StatePublished - Jul 2021

Keywords

  • Antioxidants
  • Drug carriers
  • Nanoparticles
  • Nitric oxide
  • Peripheral artery disease

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