title: Combined delivery of dexamethasone and plasmid DNA in an animal model of LPS-induced acute lung injury.
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.
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Ji Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Lee
authors.forename: Joon Sig
authors.initials: JS
authors.lastname: Choi
authors.forename: Taiyoun
authors.initials: T
authors.lastname: Rhim
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D016207:Cytokines / Q000037:antagonists & inhibitors; D004247:DNA / Q000235:genetics*; D003907:Dexamethasone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D010957:Plasmids / Q000235:genetics; D011094:Polyethyleneimine / Q000737:chemistry*; D014162:Transfection
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004337:Drug Carriers; D008070:Lipopolysaccharides; C485184:enhanced green fluorescent protein; C482199:lipopolysaccharide, E coli O55-B5; D049452:Green Fluorescent Proteins; D003907:Dexamethasone; D011094:Polyethyleneimine; D004247:DNA; D008156:Luciferases