Cationic cage-like complexes formed by DC-cholesterol, Quil-A, and phospholipid

This study describes the formation of cationic, cage-like complexes which have a structure similar to classic anionic ISCOMs. In order to prepare these complexes cholesterol, a major component of classic ISCOM formulations, was substituted with a cationic derivative, 3β-[N-(N′,N′-dimethylaminoethane...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2005-08, Vol.94 (8), p.1794-1807
Main Authors: Lendemans, Dirk G., Myschik, Julia, Hook, Sarah, Rades, Thomas
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - chemistry
Biological and medical sciences
Buffers
Cations
Chemistry, Pharmaceutical
Cholesterol - analogs & derivatives
Cholesterol - chemistry
colloids
DC-cholesterol
General pharmacology
ISCOMs
Medical sciences
micelle
Micelles
microscopy
Microscopy, Electron
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
phase diagram
Phospholipids - chemistry
Quil-A
Quillaja Saponins
Saponins - chemistry
vaccine delivery
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Summary:This study describes the formation of cationic, cage-like complexes which have a structure similar to classic anionic ISCOMs. In order to prepare these complexes cholesterol, a major component of classic ISCOM formulations, was substituted with a cationic derivative, 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl]-cholesterol (DC-CHOL). Colloidal dispersions with varying compositions of DC-CHOL, phosphatidylcholine, and Quil-A, which is a mixture of anionic triterpene saponins, were prepared by the lipid-film hydration method and characterised by transmission electron microscopy and laser Doppler electrophoresis. The colloidal structures obtained are presented in pseudo-ternary phase diagrams with two buffer systems as the pseudo-component. It was found that the formation of cationic, cage-like particles is highly depending on the formulation buffer. With TRIS buffered saline (TBS) pH 7.4, cage-like particles formed at compositions with high proportions of DC-CHOL and had a strongly positive zeta-potential. These could be purified by differential centrifugation. With phosphate buffered saline pH 7.4, the formation of cage-like particles was much reduced. It was shown that the formation of cage-like particles with a positive charge depended on suitable concentrations of TRIS in the hydration buffer.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.20394