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

Kaur, Randip, Henriksen-Lacey, Malou, Wilkhu, Jitinder, Devitt, Andrew, 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.

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. © 2013 American Chemical Society.

Publication DOI: https://doi.org/10.1021/mp400372j
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences > Chronic and Communicable Conditions
Life & Health Sciences
Life & Health Sciences > Biosciences
Life & Health Sciences > Cellular and Molecular Biomedicine
Life & Health Sciences > Cell & Tissue Biomedical Research
Additional Information: Funding: This work was partly funded by NewTBVAC (contract no. HEALTHF3-2009-241745). NewTBVAC has been made possible by contributions from the European Commission.
Uncontrolled Keywords: vaccine,subunit antigen,liposomes,DDA,bilayer fluidity,biodistribution,adjuvant,cholesterol
Full Text Link: https://strathp ... th.ac.uk/56820/
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://pubs.ac ... .1021/mp400372j (Publisher URL)
Published Date: 2014-01-06
Authors: Kaur, Randip
Henriksen-Lacey, Malou
Wilkhu, Jitinder
Devitt, Andrew ( 0000-0002-4651-6761)
Christensen, Dennis
Perrie, Yvonne

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