Combined Delivery of a Lipopolysaccharide‐Binding Peptide and the Heme Oxygenase‐1 Gene Using Deoxycholic Acid‐Conjugated Polyethylenimine for the Treatment of Acute Lung Injury

A ternary complex comprising plasmid DNA, lipopolysaccharide‐binding peptide (LBP), and deoxycholic acid‐conjugated polyethylenimine (PEI‐DA) is prepared for combinational therapy of acute lung injury (ALI). The LBP is designed as an anti‐inflammatory peptide based on the lipopolysaccharide (LPS)‐binding domain of HMGB‐1. In vitro cytokine assays show that LBP reduces levels of proinflammatory cytokines by inhibiting LPS. PEI‐DA is synthesized as the gene carrier by conjugation of deoxycholic acid to low‐molecular weight polyethylenimine (2 kDa, PEI2k). PEI‐DA has higher transfection efficiency than high‐molecular weight polyethylenimine (25 kDa, PEI25k). The ternary complex of an HO‐1 plasmid (pHO‐1), PEI‐DA, and LBP is prepared as a combinational system to deliver the therapeutic gene and peptide. The transfection efficiency of the ternary complex is higher than that of the pHO‐1/PEI‐DA binary complex. The ternary complex also reduces TNF‐α secretion in LPS‐activated Raw264.7 macrophage cells. Administration of the ternary complex into the lungs of an animal ALI model by intratracheal injection induces HO‐1 expression and reduces levels of proinflammatory cytokines more efficiently than the pHO‐1/PEI‐DA binary complex or LBP alone. In addition, the ternary complex reduces inflammation in the lungs. Therefore, the pHO‐1/PEI‐DA/LBP ternary complex may be an effective treatment for ALI. Ternary complexes for combined delivery of the heme oxygenase‐1 (HO‐1) gene and lipopolysaccharide‐binding peptide (LBP) are developed. Deoxycholic acid‐conjugated polyethylenimine (DA‐PEI) is used to make the ternary complexes. The HO‐1 gene and LBP peptide of the ternary complexes have synergistic effects in the acute lung injury (ALI) model, reducing inflammatory reaction. Thus, the pHO‐1/PEI‐DA/LBP ternary complex may be useful for the treatment of ALI.