Incorporation of the TLR4 agonist monophosphoryl lipid A into the bilayer of DDA/DTDB liposomes : physico-chemical characterization and induction of CD8+ T-Cell responses in vivo

TY - JOUR

T1 - Incorporation of the TLR4 agonist monophosphoryl lipid A into the bilayer of DDA/DTDB liposomes 

T2 - physico-chemical characterization and induction of CD8+ T-Cell responses in vivo

AU - Nordly, Pernille Juul

AU - Agger, Else Marie

AU - Andersen, Peter

AU - Nielsen, Hanne Mørck

AU - Foged, Camilla

PY - 2011/3

Y1 - 2011/3

N2 - 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. 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. 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. 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.

AB - 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. 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. 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. 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.

U2 - 10.1007/s11095-010-0301-9

DO - 10.1007/s11095-010-0301-9

M3 - Journal article

C2 - 21042837

SN - 0724-8741

VL - 28

SP - 553

EP - 562

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 3

ER -