A Nanoparticle Delivery of Plasmid Encoding Hepatocyte Growth Factor for Gene Therapy of Silicosis in Mice

J Pharm Pharm Sci. 2021:24:488-498. doi: 10.18433/jpps32218.

Abstract

Purpose: Silicosis is a serious occupational disease that is characterized by pulmonary infiltrates and fibrosis and is often refractory to current treatments. New therapeutic strategies for silicosis are needed. Hepatocyte growth factor (HGF) is a latent anti-inflammatory and anti-fibrotic growth factor.

Methods: We prepared a polyethyleneimine-polyethylene glycol/pHGF/hyaluronic acid (PEG-PEI/pHGF/HA) nanomaterials loaded with plasmid DNA encoding HGF gene to increase its transfection efficiency. The characterization, including DNA entrapment efficiency, morphology, particle size, and zeta-potential of PEG-PEI/pHGF/HA was studied. And a PEG-PEI/pHGF/HA (N/P=30:1) nanoparticle with low toxicity and high transfection efficiency was used in treatment for silicosis in mice.

Results: The results showed that the human HGF expression in the lungs of the mice was increased, and the inflammatory cell infiltration and fibrous collagen deposition was significantly reduced.

Conclusion: Therefore, PEG-PEI/pHGF/HA nanoparticle warrant further investigation and may be a potential therapeutic strategy for silicosis.

MeSH terms

  • A549 Cells
  • Animals
  • Genetic Therapy / methods*
  • Hepatocyte Growth Factor / administration & dosage*
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / therapeutic use
  • Humans
  • Lung / drug effects
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticle Drug Delivery System*
  • Plasmids / genetics
  • Silicosis / drug therapy*
  • Silicosis / pathology
  • Transfection / methods

Substances

  • Nanoparticle Drug Delivery System
  • Hepatocyte Growth Factor