Combined delivery of dexamethasone and plasmid DNA in an animal model of LPS-induced acute lung injury

J Control Release. 2011 Nov 30;156(1):60-9. doi: 10.1016/j.jconrel.2011.06.041. Epub 2011 Jul 6.

Abstract

Dexamethasone was conjugated to low molecular weight polyethylenimine (2kDa, PEI2k). Dexamethasone conjugated PEI2k (PEI2k-Dexa) was evaluated as a combined delivery carrier of dexamethasone and plasmid DNA (pDNA) in an animal model of lipopolysaccharide (LPS) induced acute lung injury (ALI). In vitro transfection of L2 lung epithelial cells, PEI2k-Dexa exhibited higher transfection efficiency than PEI2k or a simple mixture of PEI2k and dexamethasone. In addition, the PEI2k-Dexa/pβ-Luc complexes reduced the levels of pro-inflammatory cytokines in LPS activated Raw 264.7 macrophage cells. The anti-inflammatory effect of PEI2k-Dexa was higher than that of controls. The PEI2k-Dexa/pβ-Luc complexes were administered to mice via intratracheal injection. PEI2k-Dexa had higher pDNA delivery efficiency than PEI2k in the lung and decreased TNF-α and IL-6 in the lung homogenates and bronchoalveolar lavage (BAL) fluid compared with the controls. Furthermore, total protein and immunoglobulin M (IgM) concentrations in BAL fluid were reduced by the PEI2k-Dexa/pβ-Luc complexes. The intratracheal injection of the PEI2k-Dexa/pcDNA-EGFP complexes in the ALI model showed higher EGFP expression compared with PEI2k. Hematoxylin and eosin (H&E) staining showed that PEI2k-Dexa reduced inflammatory reaction in the lung. Therefore, PEI2k-Dexa may be useful for combination gene and drug therapy for ALI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / immunology
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Bronchoalveolar Lavage Fluid / immunology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cytokines / antagonists & inhibitors
  • DNA / genetics*
  • Dexamethasone / administration & dosage*
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • Drug Stability
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Gene Transfer Techniques*
  • Green Fluorescent Proteins / genetics
  • Lipopolysaccharides / pharmacology
  • Luciferases / genetics
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Microscopy, Fluorescence
  • Molecular Weight
  • Plasmids / genetics
  • Polyethyleneimine / chemistry*
  • Transfection

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drug Carriers
  • Lipopolysaccharides
  • enhanced green fluorescent protein
  • lipopolysaccharide, E coli O55-B5
  • Green Fluorescent Proteins
  • Dexamethasone
  • Polyethyleneimine
  • DNA
  • Luciferases