Journal
MOLECULAR PHARMACEUTICS
Volume 11, Issue 7, Pages 2262-2270Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp400677y
Keywords
inflammation; oxidative stress; SOD mimetic; nanocarrier; ROS; tocopherol; cytokines; targeted drug delivery; nanoparticles; antioxidants/anti-inflammatory; tocopherol/vitamin E; endothelial cells
Funding
- University of Pennsylvania Hematology T32 Training Grant [T32 HL07439]
- NIH [HL087036]
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Oxidative stress and inflammation are intertwined contributors to numerous acute vascular pathologies. A novel dual bioactive nanopartide 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-PECAN' antibody to the nanopartides provided endothelial targeting and potentiated nanopartide-mediated suppression of inflammatory activation of these cells manifested by expression of VCAM, E-selectin, and IL-8. This nanopartide technology may find applicability with drug combinations relevant for other pathologies.
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