Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents.

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.

• Authors: Flavio Dormont, Romain Brusini, Catherine Cailleau, Franceline Reynaud, Arnaud Peramo, Amandine Gendron, Julie Mougin, Françoise Gaudin, Mariana Varna, Patrick Couvreur
• Journal: Science advances (Sci Adv) Vol. 6 Issue 23 Pg. eaaz5466 (06 2020) ISSN: 2375-2548 [Electronic] United States
• PMID: 32548259 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Chemical References

• Antioxidants
• Immunologic Factors
• Lipopolysaccharides
• Squalene
• alpha-Tocopherol
• Adenosine

Topics

• Adenosine (administration & dosage, chemistry)
• Animals
• Antioxidants (administration & dosage, chemistry)
• Betacoronavirus
• COVID-19
• Coronavirus Infections (drug therapy, pathology, virology)
• Disease Models, Animal
• Drug Delivery Systems (methods)
• Endotoxemia (chemically induced, drug therapy)
• Female
• Immunologic Factors (administration & dosage, chemistry)
• Lipopolysaccharides (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Nanoparticles (administration & dosage, chemistry)
• Pandemics
• Pneumonia, Viral (drug therapy, pathology, virology)
• SARS-CoV-2
• Squalene (administration & dosage, chemistry)
• Systemic Inflammatory Response Syndrome (chemically induced, drug therapy)
• Treatment Outcome
• alpha-Tocopherol (administration & dosage, chemistry)