Abstract
Inflammation-associated thrombosis is a non-negligible source of mortalities and morbidities worldwide. To manipulate inflammation-associated coagulation, nanoparticles that contain anti-inflammatory polymer (copolyoxalate containing vanillyl alcohol, PVAX) and anti-thrombotic heparin derivative deoxycholic acid (Hep-DOCA) are prepared. The strategy takes advantage of the reducted side effects of heparin through heparin conjugation, achievement of long-term anti-inflammation by inflammation-trigged release of anti-inflammatory agents, and formation of PVAX/heparin-DOCA nanoparticles by co-self-assembly. It is demonstrated that the Hep-DOCA conjugate and PVAX are synthesized successfully; PVAX and Hep-DOCA nanodrugs (HDP) are obtained by co-assembly; the HDP nanoparticles effectively reduce the inflammation and coagulation without inducing lethal bleeding both in vivo and in vitro. The method provided here is versatile and effective, which paves new way to develop nanodrugs to treat inflammation-associated thrombosis safely.
Keywords:
copolyoxalate containing vanillyl alcohol; heparin-deoxycholic acid; inflammation-associated thrombosis; nanoparticles; reactive oxygen species-responsive.
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / pharmacology
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Antioxidants / chemical synthesis*
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Antioxidants / pharmacology
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Benzyl Alcohols / chemistry
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Biomarkers / blood
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Carrageenan / administration & dosage
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Desoxycorticosterone Acetate / chemistry
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Female
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Fibrinolytic Agents / chemical synthesis*
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Fibrinolytic Agents / pharmacology
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Heparin / chemistry
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Heparin / pharmacology*
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Inflammation
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Interleukin-10 / blood
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Interleukin-10 / immunology
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Interleukin-6 / blood
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Interleukin-6 / immunology
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Mice
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Nanoparticles / administration & dosage
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Nanoparticles / chemistry*
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Oxalic Acid / chemistry
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Polymerization
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Reactive Oxygen Species / immunology
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Reactive Oxygen Species / metabolism
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Thrombosis / chemically induced
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Thrombosis / immunology
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Thrombosis / pathology
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Thrombosis / prevention & control*
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Tumor Necrosis Factor-alpha / blood
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Tumor Necrosis Factor-alpha / immunology
Substances
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Anti-Inflammatory Agents
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Antioxidants
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Benzyl Alcohols
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Biomarkers
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Fibrinolytic Agents
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IL10 protein, mouse
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Interleukin-6
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Reactive Oxygen Species
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Tumor Necrosis Factor-alpha
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interleukin-6, mouse
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Interleukin-10
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Desoxycorticosterone Acetate
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Carrageenan
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Heparin
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Oxalic Acid
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vanillyl alcohol