CATIONIC LIPID-MEDIATED GENE DELIVERY TO MURINE LUNG - CORRELATION OFLIPID HYDRATION WITH IN-VIVO TRANSFECTION ACTIVITY

A panel of lipidic tetraalkylammonium chlorides has been prepared and screened in studies of both lipid hydration and in vivo mouse transfec tion. The effect of cationic lipid structure on liposome surface hydra tion was determined using differential scanning calorimetry. Increases in headgroup steric bulk and the inclusion of cis-unsaturation in the hydrophobic domain led to greater lipid hydration, indicative of a de crease in lipid polar domain associations. Cationic lipids containing hydrogen-bonding functionality in the polar domain exhibited a corresp onding decrease in observed lipid hydration, indicative of an increase in lipid polar domain associations. To explore a potential correlatio n of the hydration data with transfection activity, we examined the in vivo transfection activity of the lipid panel by direct intratracheal instillation of cationic liposome-DNA complexes into BALB/c mice. The more active transfection agents were the lipids that featured headgro up structures promoting close polar domain association in combination with fatty acyl cis-unsaturation. The hydration data suggest that the more effective transfection lipids for mouse lung delivery are those p ossessing the greatest imbalance between the cross-sectional areas occ upied by the polar and hydrophobic domains.