Cage-like complexes formed by DOTAP, Quil-A and cholesterol

In this note we describe the substitution of the phospholipid component in classical ISCOMs (immune-stimulating complexes) with the cationic lipid dioleoyl-trimethyl-ammonium-propane (DOTAP). The self-assembled colloidal structures formed by DOTAP, Quil-A and cholesterol were characterised using transmission electron microscopy and laser Doppler velocimetry. Samples were prepared using the lipid-film hydration and dialysis techniques. Cage-like structures containing DOTAP were obtained in high numbers using dialysis, but not lipid-film hydration on day 4 post-preparation. The formation of cage-like structures was however only observed at compositions with low weight proportions of DOTAP (less than 25%) resulting in neutral to negative ζ-potentials of the colloidal particles. Compositions with high weight proportions of DOTAP displayed phase separation phenomena. Thus, whilst DOTAP can be incorporated with Quil-A and cholesterol to form cage-like particles, it appears to be unsuitable to prepare cationic equivalents of ISCOMs.