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

Overview of attention for article published in PLOS ONE, May 2018
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3 tweeters

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17 Dimensions

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29 Mendeley
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Title
Endothelium-targeted delivery of dexamethasone by anti-VCAM-1 SAINT-O-Somes in mouse endotoxemia
Published in
PLOS ONE, May 2018
DOI 10.1371/journal.pone.0196976
Pubmed ID
Authors

Ranran Li, Piotr S. Kowalski, Henriëtte W. M. Morselt, Ilona Schepel, Rianne M. Jongman, Adnan Aslan, Marcel H. J. Ruiters, Jan G. Zijlstra, Grietje Molema, Matijs van Meurs, Jan 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 responses. Dexamethasone-loaded anti-VCAM-1 SAINT-O-Somes specifically localized at VCAM-1 expressing endothelial cells in the microvasculature of inflamed organs. This was associated with a marginal attenuation of the expression of a few pro-inflammatory genes in kidney and liver, while no effects in the lung were observed. This study reveals that, although local accumulation of the targeted drug was achieved, endothelial targeted dexamethasone containing anti-VCAM-1 SAINT-O-Somes exhibited marginal effects on inflammatory endothelial cell activation in a model of endotoxemia. Studies with more potent drugs encapsulated into anti-VCAM-1 SAINT-O-Somes will in the future reveal whether this delivery system can be further developed for efficacious endothelial directed delivery of drugs in the treatment of sepsis.

Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 5 17%
Student > Ph. D. Student 4 14%
Professor 3 10%
Unspecified 2 7%
Student > Bachelor 2 7%
Other 8 28%
Unknown 5 17%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 5 17%
Biochemistry, Genetics and Molecular Biology 5 17%
Medicine and Dentistry 5 17%
Immunology and Microbiology 3 10%
Agricultural and Biological Sciences 2 7%
Other 3 10%
Unknown 6 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 August 2018.
All research outputs
#14,111,691
of 23,056,273 outputs
Outputs from PLOS ONE
#114,540
of 196,595 outputs
Outputs of similar age
#178,671
of 326,939 outputs
Outputs of similar age from PLOS ONE
#1,870
of 3,367 outputs
Altmetric has tracked 23,056,273 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 196,595 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.2. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 326,939 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 43rd percentile – i.e., 43% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3,367 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.