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

8 Citations (Scopus)

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.

LanguageEnglish
Pages2724-2733
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume100
Issue number7
DOIs
Publication statusPublished - Jul 2011

Fingerprint

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

Keywords

  • liposomes
  • particle size
  • cationic lipids
  • threitol ceramide
  • invariant natural killer T-cells
  • dendritic cells
  • monolayer studies
  • bilayer

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.
@article{b72373ac5bbf445a94a186a96b63cb0f,
title = "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.",
keywords = "liposomes, particle size, cationic lipids, threitol ceramide, invariant natural killer T-cells, dendritic cells, monolayer studies, bilayer",
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",
note = "Copyright {\circledC} 2011 Wiley-Liss, Inc. and the American Pharmacists Association",
year = "2011",
month = "7",
doi = "10.1002/jps.22500",
language = "English",
volume = "100",
pages = "2724--2733",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
number = "7",

}

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

TY - JOUR

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

N1 - Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

PY - 2011/7

Y1 - 2011/7

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 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.

AB - 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.

KW - liposomes

KW - particle size

KW - cationic lipids

KW - threitol ceramide

KW - invariant natural killer T-cells

KW - dendritic cells

KW - monolayer studies

KW - bilayer

U2 - 10.1002/jps.22500

DO - 10.1002/jps.22500

M3 - Article

VL - 100

SP - 2724

EP - 2733

JO - Journal of Pharmaceutical Sciences

T2 - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 7

ER -