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 zeta-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.
Lendemans
D G
DG
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Egert
A M
AM
Hook
S
S
Rades
T
T
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000737:chemistry*; D003102:Colloids; D004339:Drug Compounding; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D016882:ISCOMs; D017078:Laser-Doppler Flowmetry; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D062605:Quillaja Saponins; D012503:Saponins / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D000276:Adjuvants, Immunologic; D003102:Colloids; D005229:Fatty Acids, Monounsaturated; D016882:ISCOMs; D000644:Quaternary Ammonium Compounds; D062605:Quillaja Saponins; D012503:Saponins; C046386:Quil A; D002784:Cholesterol; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane