TY - JOUR
T1 - Nano encapsulated novel compound SA-10 with therapeutic activity in both acute and chronic murine hindlimb ischemia models
AU - Hinkle, Louis
AU - Le, Duong
AU - Nguyen, Tam
AU - Tran, Vy
AU - Amankwa, Charles E.
AU - Weston, Courtney
AU - Shen, Haifa
AU - Nguyen, Kytai T.
AU - Rahimi, Maham
AU - Acharya, Suchismita
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Drug carriers
KW - Nanoparticles
KW - Nitric oxide
KW - Peripheral artery disease
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U2 - 10.1016/j.nano.2021.102400
DO - 10.1016/j.nano.2021.102400
M3 - Article
C2 - 33866011
AN - SCOPUS:85106227783
SN - 1549-9634
VL - 35
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
M1 - 102400
ER -