Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents.
Adenosine
/ administration & dosage
Animals
Antioxidants
/ administration & dosage
Betacoronavirus
COVID-19
Coronavirus Infections
/ drug therapy
Disease Models, Animal
Drug Delivery Systems
/ methods
Endotoxemia
/ chemically induced
Female
Immunologic Factors
/ administration & dosage
Lipopolysaccharides
/ pharmacology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Nanoparticles
/ administration & dosage
Pandemics
Pneumonia, Viral
/ drug therapy
SARS-CoV-2
Squalene
/ administration & dosage
Systemic Inflammatory Response Syndrome
/ chemically induced
Treatment Outcome
alpha-Tocopherol
/ administration & dosage
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
20
09
2019
accepted:
10
04
2020
entrez:
18
6
2020
pubmed:
18
6
2020
medline:
8
7
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32548259
doi: 10.1126/sciadv.aaz5466
pii: aaz5466
pmc: PMC7274527
doi:
Substances chimiques
Antioxidants
0
Immunologic Factors
0
Lipopolysaccharides
0
Squalene
7QWM220FJH
alpha-Tocopherol
H4N855PNZ1
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
eaaz5466Informations de 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).
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