A class of pyridinium-based cationic lipids was synthesized bearing C9 to C22 saturated, unsaturated straight and branched hydrocarbon chains. The available compounds present a range of values of the lipid shape parameter which was expected to control the lamellar-hexagonal phase balance in complexes with DNA. The lipid phase behavior of the lipoplexes was derived from small-angle X-ray scattering experiments and correlated with the lipid  shape parameter computed from molecular structure.  The effect of variation in structure and lipoplex formulation on DNA transfection (b-galactosidase and GFP transfection in CHO-K1 cells) and cytotoxicity of these lipids in mixtures with co-lipids was assessed.  These studies were applied to define a Transfection Index (TI) which encompasses the variation in the lipid shape parameter, the phase packing and the partition of these lipids into the lipoplex.  We show a correlation between the experimental transfection efficiency and TI. The cytotoxicity of the lipid formulations was also correlated with the shape parameter and the partition of the lipids together with the experimental charge ratio used in lipoplex formation.

Synthesis and study of pyridinium based cationic lipids as gene delivery vectors

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.