Quil A-lipid powder formulations releasing ISCOMs and related colloidal structures upon hydration
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Quil A-lipid powder formulations releasing ISCOMs and related colloidal structures upon hydration. / Demana, Patrick H; Davies, Nigel M; Hook, Sarah; Rades, Thomas.
In: Journal of controlled release : official journal of the Controlled Release Society, Vol. 103, No. 1, 02.03.2005, p. 45-59.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Quil A-lipid powder formulations releasing ISCOMs and related colloidal structures upon hydration
AU - Demana, Patrick H
AU - Davies, Nigel M
AU - Hook, Sarah
AU - Rades, Thomas
PY - 2005/3/2
Y1 - 2005/3/2
N2 - The aim of the present study was to prepare solid Quil A-cholesterol-phospholipid formulations (as powder mixtures or compressed to pellets) by physical mixing or by freeze-drying of aqueous dispersions of these components in ratios that allow spontaneous formation of ISCOMs and other colloidal structures upon hydration. The effect of addition of excess cholesterol to the lipid mixtures on the release of a model antigen (PE-FITC-OVA) from the pellets was also investigated. Physical properties were evaluated by X-ray powder diffractometry (XPRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and polarized light microscopy (PLM). Characterization of aqueous colloidal dispersions was performed by negative staining transmission electron microscopy (TEM). Physically mixed powders (with or without PE-FITC-OVA) and pellets prepared from the same powders did not spontaneously form ISCOM matrices and related colloidal structures such as worm-like micelles, ring-like micelles, lipidic/layered structures and lamellae (hexagonal array of ring-like micelles) upon hydration as expected from the pseudo-ternary diagram for aqueous mixtures of Quil A, cholesterol and phospholipid. In contrast, spontaneous formation of the expected colloids was demonstrated for the freeze-dried lipid mixtures. Pellets prepared by compression of freeze-dried powders released PE-FITC-OVA slower than those prepared from physically mixed powders. TEM investigations revealed that the antigen was released in the form of colloidal particles (ISCOMs) from pellets prepared by compression of freeze-dried powders. The addition of excess cholesterol slowed down the release of antigen. The findings obtained in this study are important for the formulation of solid Quil A-containing lipid articles as controlled particulate adjuvant containing antigen delivery systems.
AB - The aim of the present study was to prepare solid Quil A-cholesterol-phospholipid formulations (as powder mixtures or compressed to pellets) by physical mixing or by freeze-drying of aqueous dispersions of these components in ratios that allow spontaneous formation of ISCOMs and other colloidal structures upon hydration. The effect of addition of excess cholesterol to the lipid mixtures on the release of a model antigen (PE-FITC-OVA) from the pellets was also investigated. Physical properties were evaluated by X-ray powder diffractometry (XPRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and polarized light microscopy (PLM). Characterization of aqueous colloidal dispersions was performed by negative staining transmission electron microscopy (TEM). Physically mixed powders (with or without PE-FITC-OVA) and pellets prepared from the same powders did not spontaneously form ISCOM matrices and related colloidal structures such as worm-like micelles, ring-like micelles, lipidic/layered structures and lamellae (hexagonal array of ring-like micelles) upon hydration as expected from the pseudo-ternary diagram for aqueous mixtures of Quil A, cholesterol and phospholipid. In contrast, spontaneous formation of the expected colloids was demonstrated for the freeze-dried lipid mixtures. Pellets prepared by compression of freeze-dried powders released PE-FITC-OVA slower than those prepared from physically mixed powders. TEM investigations revealed that the antigen was released in the form of colloidal particles (ISCOMs) from pellets prepared by compression of freeze-dried powders. The addition of excess cholesterol slowed down the release of antigen. The findings obtained in this study are important for the formulation of solid Quil A-containing lipid articles as controlled particulate adjuvant containing antigen delivery systems.
KW - Adjuvants, Pharmaceutic
KW - Chemistry, Pharmaceutical
KW - Colloids
KW - Freeze Drying
KW - ISCOMs
KW - Lipids
KW - Powders
KW - Saponins
KW - Water
U2 - 10.1016/j.jconrel.2004.11.027
DO - 10.1016/j.jconrel.2004.11.027
M3 - Journal article
C2 - 15710499
VL - 103
SP - 45
EP - 59
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -
ID: 46408610