In vivo gene delivery to the lung using polyethylenimine and fractured polyamidoamine dendrimers

Background Gene transfer into the airways could be of importance for the tr eatment of chronic lung diseases such as cystic fibrosis. In the past few y ears several attempts have been made to effectively deliver DNA to the lung using different viral and non-viral vector systems. Viral vectors and cati onic lipids have been tested intensively but the properties of cationic pol ymers such as polyethylenimine (PEI) 25 kDa and fractured polyamidoamine de ndrimers to deliver DNA to the airways have not been studied. Surfactant pr eparations have been shown to influence pulmonary adenoviral and naked plas mid DNA mediated gene transfer in vivo. We investigated the gene delivery e fficiency of branched PEI 25 kDa and fractured dendrimers to the murine lun g in vivo and also examined the effect of surfactant on PEI 25 kDa mediated gene transfer to the lung. Methods Cationic polymer/DNA complexes were prepared in 25 mM HEPES buffer (pH = 7.4) or double distilled water and administered to the lungs of BALB/ c mice via cannula intubation. The trachea, left and right lung, heart, liv er and esophagus were examined for luciferase activity. Inflammation was as sessed by performing standard histology. Results PEI/DNA complexes showed a high level of luciferase gene expression in the lung. Complexes formed in double distilled water exhibited higher g ene expression than complexes formed in 25 mM HEPES buffer (pH 7.4). The op timal N/P ratio was found to be N/P = 10 in double distilled water. Lucifer ase activity was only detected in the lung and decreased rapidly in a time- dependent manner. The addition of a natural surfactant preparation, Alveofa ct(TM), slightly reduced gene transfer of branched PEI 25 kDa. Luciferase g ene expression obtained by using fractured dendrimers was very low. Conclusion The present study demonstrates that PEI 25 kDa, but not polyamid oamine dendrimers, effectively mediates transient gene transfer to the muri ne lung after intratracheal intubation. In conclusion, branched PEI 25 kDa was found to be an effective vector for pulmonary gene delivery in vivo, be ing superior to fractured dendrimers. Copyright (C) 2000 John Wiley & Sons, Ltd.