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Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.
Ou, An-Te; Zhang, Jia-Xin; Fang, Yue-Fei; Wang, Rong; Tang, Xue-Ping; Zhao, Peng-Fei; Zhao, Yu-Ge; Zhang, Meng; Huang, Yong-Zhuo.
  • Ou AT; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Zhang JX; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • Fang YF; Zhongshan Institute for Drug Discovery, SIMM, CAS, Zhongshan, 528437, China.
  • Wang R; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Tang XP; Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • Zhao PF; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Zhao YG; Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 501450, China.
  • Zhang M; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Huang YZ; Nanchang University College of Pharmacy, Nanchang, 330006, China.
Acta Pharmacol Sin ; 42(11): 1913-1920, 2021 11.
Article in English | MEDLINE | ID: covidwho-1437673
ABSTRACT
Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Colitis, Ulcerative / Systemic Inflammatory Response Syndrome / Disulfiram / COVID-19 / Lactoferrin Limits: Animals / Humans Language: English Journal: Acta Pharmacol Sin Journal subject: Pharmacology Year: 2021 Document Type: Article Affiliation country: S41401-021-00770-w

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Colitis, Ulcerative / Systemic Inflammatory Response Syndrome / Disulfiram / COVID-19 / Lactoferrin Limits: Animals / Humans Language: English Journal: Acta Pharmacol Sin Journal subject: Pharmacology Year: 2021 Document Type: Article Affiliation country: S41401-021-00770-w