2. Academic Validation
  3. Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases

Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases

  • Acta Pharmacol Sin. 2021 Nov;42(11):1913-1920. doi: 10.1038/s41401-021-00770-w.
An-Te Ou 1 2 3,  Jia-Xin Zhang 1 4,  Yue-Fei Fang 1 5,  Rong Wang 1 6,  Xue-Ping Tang 1 5,  Peng-Fei Zhao 1 7,  Yu-Ge Zhao 8,  Meng Zhang 9,  Yong-Zhuo Huang 10 11 12 13
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 Zhongshan Institute for Drug Discovery, SIMM, CAS, Zhongshan, 528437, China.
  • 4 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 5 Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 501450, China.
  • 6 Nanchang University College of Pharmacy, Nanchang, 330006, China.
  • 7 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • 8 Tongji University School of Medicine, Shanghai, 200092, China.
  • 9 Department of Pharmacy, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
  • 10 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. yzhuang@simm.ac.cn.
  • 11 University of Chinese Academy of Sciences, Beijing, 100049, China. yzhuang@simm.ac.cn.
  • 12 Zhongshan Institute for Drug Discovery, SIMM, CAS, Zhongshan, 528437, China. yzhuang@simm.ac.cn.
  • 13 NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, Shanghai, 201203, China. yzhuang@simm.ac.cn.
PMID: 34561552 DOI: 10.1038/s41401-021-00770-w
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.

Keywords

disulfiram; inflammation; lactoferrin; macrophage-targeting delivery; pyroptosis; sepsis; ulcerative colitis.

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