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Issue 7, 2017
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Synergic modulation of the inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine-containing polymer–lipid hybrid nanoparticles

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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 exaggerates 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-PLNPs) 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 these hybrid nanoparticles 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-PLNPs) and PS plus α-tocopherol-containing (PST-PLNPs) polymer–lipid hybrid nanoparticles significantly increased the viability of lipopolysaccharide (LPS)-treated macrophages compared with phosphatidylcholine-containing PLNPs. PST-PLNPs had a better effect than PS-PLNPs, which was attributed to the synergy between PS and α-tocopherol. This synergic action of PST-PLNPs reduced NO and pro-inflammatory cytokine (IL-6) production and increased anti-inflammatory cytokine (TGF-β1) production when incubated with activated macrophages. Thus, these self-filling biodegradable polymer–lipid hybrid nanoparticles (PST-PLNPs) containing anti-oxidant and anti-inflammatory molecules might be potential alternative drug carriers to liposomes and polymeric nanoparticles for the treatment of chronic inflammatory diseases such as ulcerative colitis.

Graphical abstract: Synergic modulation of the inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine-containing polymer–lipid hybrid nanoparticles

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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., 2017,8, 1514-1520
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    Synergic modulation of the inflammatory state of macrophages utilizing anti-oxidant and phosphatidylserine-containing polymer–lipid hybrid nanoparticles

    Md. Z. Hosain, K. Yuzuriha, Khadijah, M. Takeo, A. Kishimura, Y. Murakami, T. Mori and Y. Katayama, Med. Chem. Commun., 2017, 8, 1514
    DOI: 10.1039/C7MD00174F

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