Endothelium-targeted delivery of dexamethasone by anti-VCAM-1 SAINT-O-Somes in mouse endotoxemia

PloS One
Ranran LiJ A A M Kamps

Abstract

Microvascular endothelial cells play a pivotal role in the pathogenesis of sepsis-induced inflammatory responses and multiple organ failure. Therefore, they represent an important target for pharmacological intervention in the treatment of sepsis. Glucocorticosteroids were widely used in the treatment of sepsis but vast evidence to support their systemic use is lacking. The limited effects of glucocorticoids in the treatment of sepsis may be explained by differential effects of drug initiated NF-κB inhibition in different cell types and insufficient drug delivery in target cells. The current study aimed therefore to investigate the effects of an endothelial targeted delivery of dexamethasone in a mouse model of endotoxemia induced by two consecutive i.p. injections of lipopolysaccharide (LPS). To achieve endothelial cell specific delivery of dexamethasone, we modified SAINT-O-Somes, a new generation of liposomes that contain the cationic amphiphile SAINT-C18 (1-methyl-4-(cis-9-dioleyl) methyl-pyridinium chloride, with antibodies against vascular cell adhesion molecule-1 (VCAM-1). In LPS challenged mice, the systemic administration of free dexamethasone had negligible effects on the microvascular inflammatory endothelial respons...Continue Reading

References

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Citations

Mar 28, 2020·Cardiovascular Research·Elena V DolmatovaKathy K Griendling
Feb 27, 2020·American Journal of Respiratory and Critical Care Medicine·Jérémie JoffreHafid Ait-Oufella
Feb 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Oscar A Marcos-ContrerasVladimir R Muzykantov
Mar 4, 2021·Journal of Nanoscience and Nanotechnology·Giorgia AilunoGabriele Caviglioli

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Methods Mentioned

BETA
dynamic light scattering
FCS
fluorescence microscopy
flow cytometry
PCR
enzyme-linked immunosorbent assay

Software Mentioned

Quantimet HR600
NICOMP

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