Article

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.

Department of Pharmaceutics and Analytical Chemistry The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark.
Pharmaceutical Research (impact factor: 4.09). 11/2010; 28(3):553-62. DOI:10.1007/s11095-010-0301-9 pp.553-62
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Keywords

adjuvant system
 
bilayer structure
 
cationic liposomes
 
DDA/TDB liposomes
 
DDA/TDB liposomes changes
 
DDA/TDB/MPL liposomes
 
decreased phase transition temperature
 
delivery systems
 
favorable liposome storage stability
 
humoral response
 
immunological properties
 
improved membrane
 
liposomes
 
membrane characteristics
 
model antigen
 
poorly soluble TLR4 agonist monophosphoryl lipid
 
promising approach
 
rational vaccine adjuvant design
 
thermodynamic properties
 
Toll-like receptor