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

Kaur, Randip, Chen, Jili, Dawoodji, Amina, Cerundolo, Vincenzo, Garcia-Diaz, Yoel R., Wojno, Justyna, Cox, Liam R., Besra, Gurdyal S., Moghaddam, Behfar and Perrie, Yvonne (2011). Preparation, characterisation and entrapment of a non-glycosidic threitol ceramide into liposomes for presentation to invariant natural killer T cells. Journal of Pharmaceutical Sciences, 100 (7), pp. 2724-2733.

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 a-galactosylceramide, which stimulates the production of large quantities of interferon-gamma (IFN-?) and interleukin-4 (IL-4). However, aGalCer leads to overstimulation of iNKT cells. It has been demonstrated that the aGalCer 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-? 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.

Publication DOI: https://doi.org/10.1002/jps.22500
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences
Life & Health Sciences > Chronic and Communicable Conditions
Additional Information: © 2011, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Uncontrolled Keywords: immunologic adjuvant,cultured cells,pharmaceutical chemistry,dendritic cells,drug compounding,drug stability,galactosylceramides,humans,interferon-gamma,natural killer cells,kinetics,liposomes,particle size,phosphatidylcholines,quaternary ammonium compounds,solubility,sugar alcohols,pharmaceutical technology,Pharmaceutical Science
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://onlineli ... .22500/abstract (Publisher URL)
Published Date: 2011-07
Authors: Kaur, Randip
Chen, Jili
Dawoodji, Amina
Cerundolo, Vincenzo
Garcia-Diaz, Yoel R.
Wojno, Justyna
Cox, Liam R.
Besra, Gurdyal S.
Moghaddam, Behfar
Perrie, Yvonne

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