title: Icam-1 targeted nanogels loaded with dexamethasone alleviate pulmonary inflammation.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America; Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: M Carme Coll
authors.initials: MC
authors.lastname: Ferrer
authors.affiliation: Department of Pharmacology and Center for Targeted Therapeutics and Translational Nanomedicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Vladimir V
authors.initials: VV
authors.lastname: Shuvaev
authors.affiliation: Department of Pharmacology and Center for Targeted Therapeutics and Translational Nanomedicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Blaine J
authors.initials: BJ
authors.lastname: Zern
authors.affiliation: Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Russell J
authors.initials: RJ
authors.lastname: Composto
authors.affiliation: Department of Pharmacology and Center for Targeted Therapeutics and Translational Nanomedicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Muzykantov
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: David M
authors.initials: DM
authors.lastname: Eckmann
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D003907:Dexamethasone / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D019446:Endotoxemia / Q000188:drug therapy; D005260:Female; D005782:Gels; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry* / Q000276:immunology; D008168:Lung / Q000187:drug effects; D051379:Mice; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D011014:Pneumonia / Q000188:drug therapy*; D011487:Protein Conformation
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D005782:Gels; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone