Amphiphilic peptide carrier for the combined delivery of curcumin and plasmid DNA into the lungs.

In this study, the R7L10 peptide, which is composed of a 7-arginine stretch and a 10-leucine stretch, was evaluated as a carrier for the combined delivery of curcumin and plasmid DNA (pDNA) into the lungs. Curcumin is a natural product with anti-inflammatory and anti-tumor effects. Curcumin-loaded R7L10 (R7L10-curucmin) was prepared by an oil-in-water (O/W) emulsion/solvent evaporation method. In vitro transfection showed that R7L10-curcumin had higher transfection efficiency than R7L10. Although R7L10-curcumin had lower transfection efficiency than polyethylenimine (25 kDa, PEI25k) and lipofectamine, R7L10-curcumin had lower cytotoxicity. In gel retardation assays and heparin competition assays, R7L10-curcumin formed a more stable complex with pDNA than R7L10. The intracellular curcumin delivery efficiency of R7L10-curcumin was higher than that of curcumin only. Furthermore, R7L10-curcumin more efficiently decreased TNF-α level in lipopolysaccharide (LPS)-activated Raw264.7 macrophage cells than curcumin only. For in vivo evaluation, pDNA/R7L10-curcumin complexes were administered into mouse lungs by intratracheal instillation. The results revealed that R7L10-curcumin delivered pDNA more efficiently than R7L10, poly-L-lysine (PLL), or PEI25k. In addition, R7L10-curcumin decreased TNF-α level in lung tissues in an acute lung injury mouse model. In contrast to PEI25k, R7L10-curcumin did not show liver toxicity after intravenous injection. These results suggest that R7L10-curcumin is a useful carrier for the combined delivery of curcumin and pDNA into the lungs.