1-2-dioleoyloxy-3-(trimethylammonium)propane and Carcinoma--Large-Cell

Delivery of genes to airway mucosa would be a very valuable method for gene therapy and vaccination. However, there have been few reports on suitable gene delivery systems for administration. In this study, we use a cationic emulsion system, which is physically stable and facilitates the transfer of genes in the presence of up to 90% serum, as a mucosal gene carrier.. Cationic lipid emulsion was formulated with squalene and 1,2-dioleoyl-sn-glycero-3-trimethylammoniumpropane (DOTAP) as major components. Emulsions formed stable complexes with DNA and protected and transferred DNA to target cells against DNase I digestion in the presence of mucosal destabilizers such as heparin sulfate (a polysaccharide of the glycosaminoglycan family in mucosa) and Newfectan (a natural lung extract of bovine) in an in vitro system. In contrast, commercial liposomes and counter liposomes, made with an identical lipid composition of emulsions, failed. After in vivo intranasal instillation, the cationic emulsion showed at least 200 times better transfection activity than the liposomal carriers in both nasal tissue and lung.. These findings show that cationic emulsions can mediate gene transfection into airway epithelium, making it a good choice for transferring therapeutic genes and for genetic vaccination against an pathogenic infection via an airway route.

Topics: Carcinoma, Large Cell; Carcinoma, Squamous Cell; Cations; Cell Culture Techniques; DNA; Emulsions; Epithelial Cells; Fatty Acids, Monounsaturated; Gene Expression; Gene Transfer Techniques; Genes, Reporter; Humans; Lipids; Liposomes; Luciferases; Lung Neoplasms; Nasal Mucosa; Phosphatidylethanolamines; Plasmids; Polysorbates; Quaternary Ammonium Compounds; Squalene; Transfection; Tumor Cells, Cultured; X-Ray Diffraction