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...
Main Authors: | , , , , , |
---|---|
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 |
_version_ | 1819198681602064384 |
---|---|
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. |
first_indexed | 2024-12-23T03:04:19Z |
format | Article |
id | doaj.art-5e39f1d9f7e24a8bb220d96a423d3607 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-23T03:04:19Z |
publishDate | 2014-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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 |
work_keys_str_mv | AT mcarmecollferrer icam1targetednanogelsloadedwithdexamethasonealleviatepulmonaryinflammation AT vladimirvshuvaev icam1targetednanogelsloadedwithdexamethasonealleviatepulmonaryinflammation AT blainejzern icam1targetednanogelsloadedwithdexamethasonealleviatepulmonaryinflammation AT russelljcomposto icam1targetednanogelsloadedwithdexamethasonealleviatepulmonaryinflammation AT vladimirrmuzykantov icam1targetednanogelsloadedwithdexamethasonealleviatepulmonaryinflammation AT davidmeckmann icam1targetednanogelsloadedwithdexamethasonealleviatepulmonaryinflammation |