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 - Funding Information:
This work was supported partly by the Applied Research Seed grant (2400018) awarded to SA by UNTHSC and by National Institutes of Health to KTN (R15 HL156076 and T32 HL 134613) and by George and Angelina Kostas grant to MR and HS.
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
VL - 35
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
SN - 1549-9634
M1 - 102400
ER -