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Synergic modulation of inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine containing polymer-lipid hybrid nanoparticles

Abstract

Inflammatory activation of macrophages is a key factor in chronic inflammatory diseases such as ulcerative colitis. The excessive production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) by macrophages causes oxidative stress during the inflammatory response and exaggerating inflammatory lesions in ulcerative colitis. Inhibition of the inflammatory activation of macrophages is a promising treatment for chronic inflammatory diseases. Here, we prepared self-filling polymer-lipid hybrid nanoparticles (PST-PLNP) consisting of poly DL-lactic acid as a hydrophobic biodegradable polymer core encapsulating α-tocopherol (T), and phosphatidylserine (PS) both on the surface and interior of the particle. We confirmed the anti-inflammatory response of this hybrid nanoparticle in activated murine macrophages. PS has anti-inflammatory effects on macrophages by modulating the macrophage phenotype, while α-tocopherol is an antioxidant that neutralizes ROS. We found that PS-containing (PS-PLNP) and PS plus α-tocopherol (PST-PLNP) containing polymer-lipid hybrid nanoparticles significantly increased the viability of lipopolysaccharide (LPS) treated macrophages compared with phosphatidylcholine containing PLNP. PST-PLNP had a better effect than PS-PLNP, which was attributed to synergy between PS and α-tocopherol. This synergic action of PST-PLNP reduced NO and pro-inflammatory cytokine (IL-6) production and increased anti-inflammatory cytokine (TGF-β1) production when incubated with activated macrophages. Thus, this self-filling biodegradable polymer-lipid hybrid nanoparticle (PST-PLNP) containing an anti-oxidant and anti-inflammatory molecules might be a potential alternative drug to liposomes and polymeric nanoparticles for the treatment of chronic inflammatory diseases such as ulcerative colitis.

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Publication details

The article was received on 08 Apr 2017, accepted on 02 Jun 2017 and first published on 02 Jun 2017


Article type: Research Article
DOI: 10.1039/C7MD00174F
Citation: Med. Chem. Commun., 2017, Accepted Manuscript
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    Synergic modulation of inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine containing polymer-lipid hybrid nanoparticles

    M. Z. Hosain, K. Yuzuriha, K. Zai, M. Takeo, A. Kishimura, Y. Murakami, T. Mori and Y. Katayama, Med. Chem. Commun., 2017, Accepted Manuscript , DOI: 10.1039/C7MD00174F

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