Abstract
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, 3beta-[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.
Original language | English |
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Journal | Journal of Pharmaceutical Sciences |
Volume | 94 |
Issue number | 8 |
Pages (from-to) | 1794-807 |
Number of pages | 14 |
ISSN | 0022-3549 |
DOIs | |
Publication status | Published - 2005 |
Externally published | Yes |
Keywords
- Adjuvants, Immunologic
- Buffers
- Cations
- Chemistry, Pharmaceutical
- Cholesterol
- Micelles
- Microscopy, Electron
- Particle Size
- Phospholipids
- Saponins