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

• Published in: International journal of pharmaceutics Vol. 332; no. 1; pp. 192 - 195
• Main Authors: Lendemans, D.G., Egert, A.M., Hook, S., Rades, T.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 06.03.2007; Elsevier
• Subjects: Adjuvants, Immunologic - chemistry; Biological and medical sciences; Cationic; Chemistry, Pharmaceutical; Cholesterol; Cholesterol - chemistry; Colloids; DOTAP; Drug Compounding; Fatty Acids, Monounsaturated - chemistry; General pharmacology; ISCOMs; Laser-Doppler Flowmetry; Medical sciences; Microscopy, Electron, Transmission; Models, Chemical; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Quaternary Ammonium Compounds - chemistry; Quil-A; Quillaja Saponins; Saponins - chemistry; Technology, Pharmaceutical - methods; Time Factors; Vaccine delivery; Quil-A; Cationic; DOTAP; Vaccine delivery; Cholesterol; ISCOMs; Quillaja saponins; Pharmaceutical technology; Cations; Vaccine; Saponin
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.09.029

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.