Targeting to Endothelial Cells Augments the Protective
Effect of Novel Dual Bioactive Antioxidant/Anti-Inflammatory Nanoparticles
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Abstract
Oxidative stress and inflammation
are intertwined contributors
to numerous acute vascular pathologies. A novel dual bioactive nanoparticle
with antioxidant/anti-inflammatory properties was developed based
on the interactions of tocopherol phosphate and the manganese porphyrin
SOD mimetic, MnTMPyP. The size and drug incorporation efficiency were
shown to be dependent on the amount of MnTMPyP added as well as the
choice of surfactant. MnTMPyP was shown to retain its SOD-like activity
while in intact particles and to release in a slow and controlled
manner. Conjugation of anti-PECAM antibody to the nanoparticles provided
endothelial targeting and potentiated nanoparticle-mediated suppression
of inflammatory activation of these cells manifested by expression
of VCAM, E-selectin, and IL-8. This nanoparticle technology may find
applicability with drug combinations relevant for other pathologies