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Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents.
Dormont, Flavio; Brusini, Romain; Cailleau, Catherine; Reynaud, Franceline; Peramo, Arnaud; Gendron, Amandine; Mougin, Julie; Gaudin, Françoise; Varna, Mariana; Couvreur, Patrick.
  • Dormont F; Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
  • Brusini R; Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
  • Cailleau C; Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
  • Reynaud F; Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
  • Peramo A; School of Pharmacy, Federal University of Rio de Janeiro, 21944-59 Rio de Janeiro, Brazil.
  • Gendron A; Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
  • Mougin J; Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
  • Gaudin F; Institut Galien Paris-Sud, CNRS UMR 8612, Université Paris-Sud, Université Paris-Saclay, 92296 Châtenay-Malabry, France.
  • Varna M; Plateforme d'Histologie Immunopathologie de Clamart (PHIC) Université Paris-Saclay, Inserm, CNRS, Institut Paris Saclay d'Innovation thérapeutique, 92296 Châtenay-Malabry, France.
  • Couvreur P; Université Paris-Saclay, Inserm, Inflammation, Microbiome and Immunosurveillance, 92140 Clamart, France.
Sci Adv ; 6(23): eaaz5466, 2020 06.
Article in English | MEDLINE | ID: covidwho-602279
ABSTRACT
Uncontrolled inflammatory processes are at the root of numerous pathologies. Most recently, studies on confirmed COVID-19 cases have suggested that mortality might be due to virally induced hyperinflammation. Uncontrolled pro-inflammatory states are often driven by continuous positive feedback loops between pro-inflammatory signaling and oxidative stress, which cannot be resolved in a targeted manner. Here, we report on the development of multidrug nanoparticles for the mitigation of uncontrolled inflammation. The nanoparticles are made by conjugating squalene, a natural lipid, to adenosine, an endogenous immunomodulator, and then encapsulating α-tocopherol, as antioxidant. This resulted in high drug loading, biocompatible, multidrug nanoparticles. By exploiting the endothelial dysfunction at sites of acute inflammation, these multidrug nanoparticles delivered the therapeutic agents in a targeted manner, conferring survival advantage to treated animals in models of endotoxemia. Selectively delivering adenosine and antioxidants together could serve as a novel therapeutic approach for safe treatment of acute paradoxal inflammation.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Squalene / Drug Delivery Systems / Systemic Inflammatory Response Syndrome / Endotoxemia / Nanoparticles Type of study: Prognostic study Language: English Journal: Sci Adv Year: 2020 Document Type: Article Affiliation country: Sciadv.aaz5466

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Squalene / Drug Delivery Systems / Systemic Inflammatory Response Syndrome / Endotoxemia / Nanoparticles Type of study: Prognostic study Language: English Journal: Sci Adv Year: 2020 Document Type: Article Affiliation country: Sciadv.aaz5466