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

Randip Kaur, Malou Henriksen-Lacey, Jitinder Wilkhu, Andrew Devitt, Dennis Christensen, Yvonne Perrie

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)197-207
Number of pages11
JournalMolecular Pharmaceutics
Volume11
Issue number1
Early online date20 Nov 2013
DOIs
Publication statusPublished - 6 Jan 2014

Bibliographical note

Funding: This work was partly funded by NewTBVAC (contract no. HEALTHF3-2009-241745). NewTBVAC has been made possible by contributions from the European Commission.

Keywords

  • vaccine
  • subunit antigen
  • liposomes
  • DDA
  • bilayer fluidity
  • biodistribution
  • adjuvant
  • cholesterol

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  • Student Theses

    Formulation and development of cationic liposomes as adjuvants for subunit protein vaccinese

    Author: Henriksen, A., 1 Feb 2011

    Supervisor: Perrie, Y. (Supervisor) & Devitt, A. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

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    Liposomes : Formulation and characterisation as contrast agents and as vaccine delivery systems

    Author: Kaur, R., May 2011

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Non-ionic surfactant technology for the delivery and administration of sub-unit flu antigens

    Author: Wilkhu, J., 12 Jun 2013

    Supervisor: Perrie, Y. (Supervisor) & Mohammed, A. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

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