caa a22 4500 445312769 CHVBK 20180317142636.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s11095-010-0301-9 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0301-9 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 [Elektronische Daten] [Pernille Nordly, Else Agger, Peter Andersen, Hanne Nielsen, Camilla Foged] 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. 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. Springer Science+Business Media, LLC, 2010 dimethyldioctadecylammonium (DDA) nationallicence liposome nationallicence monophosphoryl lipid A (MPL) nationallicence trehalose 6,6-dibehenate (TDB) nationallicence vaccine nationallicence Nordly Pernille Department of Pharmaceutics and Analytical Chemistry The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark aut Agger Else Department of Infectious Disease Immunology, Vaccine Delivery & Formulation, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark aut Andersen Peter Department of Infectious Disease Immunology, Vaccine Delivery & Formulation, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark aut Nielsen Hanne Department of Pharmaceutics and Analytical Chemistry The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark aut Foged Camilla Department of Pharmaceutics and Analytical Chemistry The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 553-562 0724-8741 28:3<553 2011 28 11095 https://doi.org/10.1007/s11095-010-0301-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0301-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nordly Pernille Department of Pharmaceutics and Analytical Chemistry The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark aut NATIONALLICENCE 700 1- Agger Else Department of Infectious Disease Immunology, Vaccine Delivery & Formulation, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark aut NATIONALLICENCE 700 1- Andersen Peter Department of Infectious Disease Immunology, Vaccine Delivery & Formulation, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark aut NATIONALLICENCE 700 1- Nielsen Hanne Department of Pharmaceutics and Analytical Chemistry The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark aut NATIONALLICENCE 700 1- Foged Camilla Department of Pharmaceutics and Analytical Chemistry The Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100, Copenhagen Ø, Denmark aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 553-562 0724-8741 28:3<553 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer