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Preparation, characterisation and entrapment of a non-glycosidic threitol ceramide into liposomes for presentation to invariant natural killer T cells

Abstract:
Dendritic cells (DCs) are able to present glycolipids to invariant natural killer T (iNKT) cells in vivo. Very few compounds have been found to stimulate iNKT cells, and of these, the best characterised is the glycolipid α-galactosylceramide, which stimulates the production of large quantities of interferon-gamma (IFN-γ) and interleukin-4 (IL-4). However, αGalCer leads to overstimulation of iNKT cells. It has been demonstrated that the αGalCer analogue, threitol ceramide (ThrCer 2), successfully activates iNKT cells and overcomes the problematic iNKT cell activation-induced anergy. In this study, ThrCer 2 has been inserted into the bilayers of liposomes composed of a neutral lipid, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), or dimethyldioctadecylammonium bromide (DDA), a cationic lipid. Incorporation efficiencies of ThrCer within the liposomes was 96% for DSPC liposomes and 80% for DDA liposomes, with the vesicle size (large multilamellar vs. small unilamellar vesicles) making no significant difference. Langmuir-Blodgett studies suggest that both DSPC and DDA stack within the monolayer co-operatively with the ThrCer molecules with no condensing effect. In terms of cellular responses, IFN-γ secretion was higher for cells treated with small DDA liposomes compared with the other liposome formulations, suggesting that ThrCer encapsulation in this liposome formulation resulted in a higher uptake by DCs. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association.

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Publisher copy:
10.1002/jps.22500

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
Weatherall Insti. of Molecular Medicine
Role:
Author


Journal:
Journal of Pharmaceutical Sciences More from this journal
Volume:
100
Issue:
7
Pages:
2724-2733
Publication date:
2011-07-01
DOI:
EISSN:
1520-6017
ISSN:
0022-3549


Language:
English
Keywords:
Pubs id:
pubs:149819
UUID:
uuid:61614091-ce11-4a1a-a9dc-78c27554635b
Local pid:
pubs:149819
Source identifiers:
149819
Deposit date:
2012-12-19

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