ICAM-1 Targeted Nanogels Loaded with Dexamethasone Alleviate Pulmonary InflammationReportar como inadecuado

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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-1ICAM-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 125IIgG. 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.

Autor: M. Carme Coll Ferrer, Vladimir V. Shuvaev, Blaine J. Zern, Russell J. Composto, Vladimir R. Muzykantov, David M. Eckmann

Fuente: http://plos.srce.hr/


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