Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.

Lysozyme dextran nanogels (NG) have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with "stealth" properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a d...

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Main Authors: M Carme Coll Ferrer, Vladimir V Shuvaev, Blaine J Zern, Russell J Composto, Vladimir R Muzykantov, David M Eckmann
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4096597?pdf=render
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author M Carme Coll Ferrer
Vladimir V Shuvaev
Blaine J Zern
Russell J Composto
Vladimir R Muzykantov
David M Eckmann
author_facet M Carme Coll Ferrer
Vladimir V Shuvaev
Blaine J Zern
Russell J Composto
Vladimir R Muzykantov
David M Eckmann
author_sort M Carme Coll Ferrer
collection DOAJ
description Lysozyme dextran nanogels (NG) have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with "stealth" properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab) directed to Intercellular Adhesion Molecule-1(ICAM-NG), whereas IgG conjugated NG (IgG-NG) are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV) injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i) ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG); and, ii) DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation.
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spelling doaj.art-5e39f1d9f7e24a8bb220d96a423d36072022-12-21T18:02:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10232910.1371/journal.pone.0102329Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.M Carme Coll FerrerVladimir V ShuvaevBlaine J ZernRussell J CompostoVladimir R MuzykantovDavid M EckmannLysozyme dextran nanogels (NG) have great potential in vitro as a drug delivery platform, combining simple chemistry with rapid uptake and cargo release in target cells with "stealth" properties and low toxicity. In this work, we study for the first time the potential of targeted NG as a drug delivery platform in vivo to alleviate acute pulmonary inflammation in animal model of LPS-induced lung injury. NG are targeted to the endothelium via conjugation with an antibody (Ab) directed to Intercellular Adhesion Molecule-1(ICAM-NG), whereas IgG conjugated NG (IgG-NG) are used for control formulations. The amount of Ab conjugated to the NG and distribution in the body after intravenous (IV) injection have been quantitatively analyzed using a tracer isotope-labeled [125I]IgG. As a proof of concept, Ab-NG are loaded with dexamethasone, an anti-inflammatory therapeutic, and the drug uptake and release kinetics are measured by HPLC. In vivo studies in mice showed that: i) ICAM-NG accumulates in mouse lungs (∼120% ID/g vs ∼15% ID/g of IgG-NG); and, ii) DEX encapsulated in ICAM-NG, but not in IgG-NG practically blocks LPS-induced overexpression of pro-inflammatory cell adhesion molecules including ICAM-1 in the pulmonary inflammation.http://europepmc.org/articles/PMC4096597?pdf=render
spellingShingle M Carme Coll Ferrer
Vladimir V Shuvaev
Blaine J Zern
Russell J Composto
Vladimir R Muzykantov
David M Eckmann
Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
PLoS ONE
title Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
title_full Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
title_fullStr Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
title_full_unstemmed Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
title_short Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
title_sort icam 1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation
url http://europepmc.org/articles/PMC4096597?pdf=render
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AT russelljcomposto icam1targetednanogelsloadedwithdexamethasonealleviatepulmonaryinflammation
AT vladimirrmuzykantov icam1targetednanogelsloadedwithdexamethasonealleviatepulmonaryinflammation
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