Journal
BIOMATERIALS
Volume 34, Issue 33, Pages 8478-8490Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.07.062
Keywords
Hyaluronic acid; Flt1 peptide; Dexamethasone; Nanoparticle; Pulmonary delivery; Asthma
Funding
- Converging Research Center Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2009-0081871, 2011-0016474]
- Korea Healthcare Technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A080711]
- NRF
- MEST [2012R1A2A2A06045773]
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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.
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