Cationic cage-like complexes formed by DC-cholesterol, Quil-A, and phospholipid
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Cationic cage-like complexes formed by DC-cholesterol, Quil-A, and phospholipid. / Lendemans, Dirk G; Myschik, Julia; Hook, Sarah; Rades, Thomas.
In: Journal of Pharmaceutical Sciences, Vol. 94, No. 8, 2005, p. 1794-807.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Cationic cage-like complexes formed by DC-cholesterol, Quil-A, and phospholipid
AU - Lendemans, Dirk G
AU - Myschik, Julia
AU - Hook, Sarah
AU - Rades, Thomas
N1 - (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Adjuvants, Immunologic
KW - Buffers
KW - Cations
KW - Chemistry, Pharmaceutical
KW - Cholesterol
KW - Micelles
KW - Microscopy, Electron
KW - Particle Size
KW - Phospholipids
KW - Saponins
U2 - 10.1002/jps.20394
DO - 10.1002/jps.20394
M3 - Journal article
C2 - 15986471
VL - 94
SP - 1794
EP - 1807
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 8
ER -
ID: 40357638