Affiliation:
1. The Second Affiliated Hospital of
Xuzhou Medical University, 32 Meijian Road, Xuzhou, Jiangsu, 221006, China
2. Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, China
Abstract
Background:
Pulmonary fibrosis (PF) is a chronic and progressive interstitial lung disease.
There is no effective treatment for PF. Hepatocyte growth factor (HGF) has anti-inflammatory and antifibrotic
effects but has limited potential owing to its short half-life.
Methods:
To increase the transfection efficiency of pVAX-HGF, we prepared polyethyleneiminepolyethylene
glycol: polyethyleneimine/pVAX-HGF (PEG-PEI: PEI/pVAX-HGF) nanocomposite
loaded with a plasmid encoding the HGF gene. The PEG-PEI:PEI/pVAX-HGF characteristics, including
morphology, particle size, zeta-potential, and DNA entrapment efficiency, were investigated. The
pVAX-HGF nanocomposites with low toxicity and high transfection efficiency were screened by cell
viability assay and cell transfection. The antifibrotic effect of pVAX-HGF nanocomposite on PF rats
induced by bleomycin (BLM) was evaluated by pulmonary function measurement, pathological examination
and collagen content assay.
Results:
Different nanocomposites were prepared to deliver pVAX-HGF, in which mix1 (PEGPEI:
PEI/pVAX-HGF) has lower potential and better entrapment ability. PEG-PEI:PEI/pVAX-HGF
(N/P=25) nanocomposite with low toxicity and high transfection efficiency was administered to PF
rats. After treatment with mix 1/pVAX-HGF, the index of lung function(including EF50, MV, TV, PEF
and PIF) in mix 1/pVAX-HGF group was higher than that of the PF group. The number of cells in
BALF of the mix 1/pVAX-HGF group was significantly lower than that of the PF groups, and the content
of hydroxyproline(HYP) and collagen Type I (Col-I) in the lung of the mix 1/pVAX-HGF group
was much lower than that of the PF groups in the early stage. The result of pathological examination
showed that rats in the mix1/pVAX-HGF group showed obviously reduced alveolar septal thickening,
fewer infiltrated inflammatory cells and less collagen deposition.
Conclusion:
The PEG-PEI:PEI/pVAX-HGF nanocomposite can ameliorate PF induced by BLM. The
pVAX-HGF nanocomposite is a latent therapeutic strategy for PF.
Publisher
Bentham Science Publishers Ltd.