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

Randip Kaur, Jili Chen, Amina Dawoodji, Vincenzo Cerundolo, Yoel R. Garcia-Diaz, Justyna Wojno, Liam R. Cox, Gurdyal S. Besra, Behfar Moghaddam, Yvonne Perrie

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages2724-2733
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number7
Early online date31 Jan 2011
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Natural Killer T-Cells
Ceramides
Liposomes
Phosphorylcholine
Glycolipids
Dendritic Cells
Interferon-gamma
Galactosylceramides
Lipids
Unilamellar Liposomes
threitol
Interleukin-4
dimethyldioctadecylammonium

Bibliographical note

© 2011, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

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

Cite this

Kaur, Randip ; Chen, Jili ; Dawoodji, Amina ; Cerundolo, Vincenzo ; Garcia-Diaz, Yoel R. ; Wojno, Justyna ; Cox, Liam R. ; Besra, Gurdyal S. ; Moghaddam, Behfar ; Perrie, Yvonne. / Preparation, characterisation and entrapment of a non-glycosidic threitol ceramide into liposomes for presentation to invariant natural killer T cells. In: Journal of Pharmaceutical Sciences. 2011 ; Vol. 100, No. 7. pp. 2724-2733.
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author = "Randip Kaur and Jili Chen and Amina Dawoodji and Vincenzo Cerundolo and Garcia-Diaz, {Yoel R.} and Justyna Wojno and Cox, {Liam R.} and Besra, {Gurdyal S.} and Behfar Moghaddam and Yvonne Perrie",
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Kaur, R, Chen, J, Dawoodji, A, Cerundolo, V, Garcia-Diaz, YR, Wojno, J, Cox, LR, Besra, GS, Moghaddam, B & Perrie, Y 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, vol. 100, no. 7, pp. 2724-2733. https://doi.org/10.1002/jps.22500

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; Perrie, Yvonne.

In: Journal of Pharmaceutical Sciences, Vol. 100, No. 7, 07.2011, p. 2724-2733.

Research output: Contribution to journalArticle

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T1 - Preparation, characterisation and entrapment of a non-glycosidic threitol ceramide into liposomes for presentation to invariant natural killer T cells

AU - Kaur, Randip

AU - Chen, Jili

AU - Dawoodji, Amina

AU - Cerundolo, Vincenzo

AU - Garcia-Diaz, Yoel R.

AU - Wojno, Justyna

AU - Cox, Liam R.

AU - Besra, Gurdyal S.

AU - Moghaddam, Behfar

AU - Perrie, Yvonne

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PY - 2011/7

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N2 - 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.

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KW - immunologic adjuvant

KW - cultured cells

KW - pharmaceutical chemistry

KW - dendritic cells

KW - drug compounding

KW - drug stability

KW - galactosylceramides

KW - humans

KW - interferon-gamma

KW - natural killer cells

KW - kinetics

KW - liposomes

KW - particle size

KW - phosphatidylcholines

KW - quaternary ammonium compounds

KW - solubility

KW - sugar alcohols

KW - pharmaceutical technology

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