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.
Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Republic of Korea.
Ji Hwan
JH
Park
Hyun Ah
HA
Kim
Jin Hyeong
JH
Park
Minhyung
M
Lee
D055371:Acute Lung Injury / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004247:DNA / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D023282:Nuclease Protection Assays; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004337:Drug Carriers; D010455:Peptides; D013501:Surface-Active Agents; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D003850:Deoxyribonuclease I; D003474:Curcumin