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Bioimaging and pulmonary applications of self-assembled Flt1 peptide-hyaluronic acid conjugate nanoparticles

Title
Bioimaging and pulmonary applications of self-assembled Flt1 peptide-hyaluronic acid conjugate nanoparticles
Authors
Kim, HPark, HTTae, YMKong, WHSung, DKHwang, BWKim, KSKim, YKHahn, SK
POSTECH Authors
Kim, YKHahn, SK
Date Issued
Nov-2013
Publisher
ELSEVIER SCI LTD
Abstract
Despite wide exploitation of corticosteroid drugs for the treatment of asthma, the poor therapeutic effect on a neutrophilic subtype of asthma prohibits the full recovery of asthma patients. In this work, dexamethasone (Dexa) was loaded in Flt1 peptide-hyaluronic acid (HA) conjugate nanoparticles to overcome the limitation of corticosteroid resistance for the treatment of neutrophilic pulmonary inflammation. Fin peptide-HA conjugates are self-assembled to nanoparticles because of hydrophobic Flt1 peptide conjugated to HA by benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) chemistry. In vitro bioimaging showed efficient internalization of Fin peptide-HA conjugate nanoparticles into lung epithelial cells by HA-receptor mediated endocytosis. Also, ex vivo imaging for the biodistribution in ICR mice revealed long-term retention of Flt1 peptide-HA conjugate nanoparticles in deep lung tissues possibly due to mucoadhesive property of HA. On the basis of bioimaging results for pulmonary drug delivery applications, we prepared Dexa-loaded Flt1 peptide-HA conjugate nanoparticles. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the formation of nanoparticles, which reduced cytokine levels of lipopolysaccharide (LPS)-stimulated cells more efficiently than free Dexa. Furthermore, according to the bronchoalveolar lavage (BAL) cellularity and histological analysis, Dexa loaded Flt1 peptide-HA conjugate nanoparticles showed remarkable therapeutic effects in both eosinophilic and neutrophilic asthma model mice. (C) 2013 Elsevier Ltd. All rights reserved.
Keywords
Hyaluronic acid; Flt1 peptide; Dexamethasone; Nanoparticle; Pulmonary delivery; Asthma; ENDOTHELIAL GROWTH-FACTOR; ANTI-FLT1 PEPTIDE; LUNG INJURY; ASTHMA; DELIVERY; RECEPTOR; TYPE-1; CELLS; NEOVASCULARIZATION; POLARIZATION
URI
http://oasis.postech.ac.kr/handle/2014.oak/13886
DOI
10.1016/J.BIOMATERIALS.2013.07.062
ISSN
0142-9612
Article Type
Article
Citation
BIOMATERIALS, vol. 34, no. 33, page. 8478 - 8490, 2013-11
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 HAHN, SEI KWANG
Dept of Materials Science & Enginrg
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