Effect of incorporating cholesterol into DDA:TDB liposomal adjuvants on bilayer properties, biodistribution, and immune responses

Kaur, Randip and Henriksen-Lacey, Malou and Wilkhu, Jitinder and Devitt, Andrew and Christensen, Dennis and Perrie, Yvonne (2014) Effect of incorporating cholesterol into DDA:TDB liposomal adjuvants on bilayer properties, biodistribution, and immune responses. Molecular Pharmaceutics, 11 (1). pp. 197-207. ISSN 1543-8384 (https://doi.org/10.1021/mp400372j)

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Abstract

Cholesterol is an abundant component of mammalian cell membranes and has been extensively studied as an artificial membrane stabilizer in a wide range of phospholipid liposome systems. In this study, the aim was to investigate the role of cholesterol in cationic liposomal adjuvant system based on dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB) which has been shown as a strong adjuvant system for vaccines against a wide range of diseases. Packaging of cholesterol within DDA:TDB liposomes was investigated using differential scanning calorimetery and surface pressure-area isotherms of lipid monolayers; incorporation of cholesterol into liposomal membranes promoted the formation of a liquid-condensed monolayer and removed the main phase transition temperature of the system, resulting in an increased bilayer fluidity and reduced antigen retention in vitro. In vivo biodistribution studies found that this increase in membrane fluidity did not alter deposition of liposomes and antigen at the site of injection. In terms of immune responses, early (12 days after immunization) IgG responses were reduced by inclusion of cholesterol; thereafter there were no differences in antibody (IgG, IgG1, IgG2b) responses promoted by DDA:TDB liposomes with and without cholesterol. However, significantly higher levels of IFN-gamma were induced by DDA:TDB liposomes, and liposome uptake by macrophages in vitro was also shown to be higher for DDA:TDB liposomes compared to their cholesterol-containing counterparts, suggesting that small changes in bilayer mechanics can impact both cellular interactions and immune responses.

  • Item type:Article
    ID code:56820
    Dates:
    Date
    Event
    6 January 2014
    Published
    30 October 2013
    Published Online
    Notes:This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/mp400372j
    Subjects:Medicine > Therapeutics. Pharmacology
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:04 Jul 2016 10:28
    Last modified:11 Nov 2024 11:24
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/56820
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