Bioimaging and pulmonary applications of self-assembled Flt1 peptide-hyaluronic acid conjugate nanoparticles.
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. Flt1 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 Flt1 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.
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Republic of Korea.
Hyemin
H
Kim
Hyun Taek
HT
Park
You Me
YM
Tae
Won Ho
WH
Kong
Dong Kyung
DK
Sung
Byung Woo
BW
Hwang
Ki Su
KS
Kim
Yoon Keun
YK
Kim
Sei Kwang
SK
Hahn
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003907:Dexamethasone / Q000737:chemistry; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*
D003907:Dexamethasone; D006820:Hyaluronic Acid
Asthma; Dexamethasone; Flt1 peptide; Hyaluronic acid; Nanoparticle; Pulmonary delivery