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, 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.
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Dirk G
DG
Lendemans
Julia
J
Myschik
Sarah
S
Hook
Thomas
T
Rades
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D002021:Buffers; D002412:Cations; D002626:Chemistry, Pharmaceutical; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry; D008823:Micelles; D008854:Microscopy, Electron; D010316:Particle Size; D010743:Phospholipids / Q000737:chemistry*; D062605:Quillaja Saponins; D012503:Saponins / Q000737:chemistry*
D000276:Adjuvants, Immunologic; D002021:Buffers; D002412:Cations; D008823:Micelles; D010743:Phospholipids; D062605:Quillaja Saponins; D012503:Saponins; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; C046386:Quil A; D002784:Cholesterol