Aerosolization of cationic lipid-DNA complexes: lipoplex characterization and optimization of aerosol delivery conditions

This study deals with the development of gene therapy in the treatment of l ung diseases. It reports on the use of ultrasonic nebulization to administe r plasmid-ipid complexes to the lungs of mice to transfect their epithelial cells. A plasmid complexed to cationic lipids was aeosolized using an ultr asonic nebulizer. We then characterized the lipoplex size and visualized th e lipoplex by electron microscopy. Finally, we assessed the in vivo transge ne expression in the lungs further to the aerosolization of different lipid -plasmid formulations. The nebulizer-generated particles were small and loo ked like a string composed of little and more or less cubic units. Transgen e expression was detected in the lungs of mice further to a 20-min exposure to aerosol particles produced with the ultrasonic nebulizer. The results o btained with our optimized plasmid-ipid-NaCl formulation suggest that this route can be used to administer an appropriate gene to the airways for the treatment of respiratory disorders. (C) 2001 Academic Press.