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Incorporation of the TLR4 agonist monophosphoryl lipid A into the bilayer of DDA/TDB liposomes: physico-chemical characterization and induction of CD8+ T-cell responses in vivo.
- Source :
-
Pharmaceutical research [Pharm Res] 2011 Mar; Vol. 28 (3), pp. 553-62. Date of Electronic Publication: 2010 Nov 02. - Publication Year :
- 2011
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Abstract
- Purpose: The combination of delivery systems like cationic liposomes and immunopotentiators such as Toll-like receptor (TLR) ligands is a promising approach for rational vaccine adjuvant design. The purpose of this study was to investigate how the incorporation of the poorly soluble TLR4 agonist monophosphoryl lipid A (MPL) into cationic liposomes based on dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB) influenced the physicochemical and immunological properties of the liposomes.<br />Methods: The DDA/TDB/MPL liposomes were characterized with regard to particle size, poly dispersity, surface charge, stability and thermodynamic properties. The adjuvant formulations were tested in vivo in mice using ovalbumin (OVA) as model antigen.<br />Results: Integration of MPL into the bilayer structure of DDA/TDB liposomes was evident from a decreased phase transition temperature, an improved membrane packing, and a reduction in surface charge. The particle size and favorable liposome storage stability were not affected by MPL. In mice, DDA/TDB/MPL liposomes induced an antigen-specific CD8(+) T-cell response and a humoral response.<br />Conclusions: Enhancing the solubility of MPL by inclusion into the bilayer of DDA/TDB liposomes changes the membrane characteristics of the adjuvant system and provides the liposomes with CD8(+) T-cell inducing properties without compromising humoral responses.
- Subjects :
- Animals
CD8-Positive T-Lymphocytes drug effects
Chemical Phenomena
Female
Lipid A metabolism
Lipid A pharmacology
Liposomes metabolism
Liposomes pharmacology
Mice
Mice, Inbred C57BL
Toll-Like Receptor 4 metabolism
CD8-Positive T-Lymphocytes metabolism
Glycolipids metabolism
Lipid A analogs & derivatives
Lipid Bilayers metabolism
Lymphocyte Activation drug effects
Quaternary Ammonium Compounds metabolism
Toll-Like Receptor 4 agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1573-904X
- Volume :
- 28
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 21042837
- Full Text :
- https://doi.org/10.1007/s11095-010-0301-9