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.
authors.affiliation: School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
authors.forename: Randip
authors.initials: R
authors.lastname: Kaur
authors.forename: Jili
authors.initials: J
authors.lastname: Chen
authors.forename: Amina
authors.initials: A
authors.lastname: Dawoodji
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Yoel R
authors.initials: YR
authors.lastname: Garcia-Diaz
authors.forename: Justyna
authors.initials: J
authors.lastname: Wojno
authors.forename: Liam R
authors.initials: LR
authors.lastname: Cox
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Behfar
authors.initials: B
authors.lastname: Moghaddam
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Perrie
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004339:Drug Compounding; D004355:Drug Stability; D005699:Galactosylceramides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007700:Kinetics; D008081:Liposomes; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012995:Solubility; D013402:Sugar Alcohols / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; D008081:Liposomes; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; D013402:Sugar Alcohols; C493154:alpha-galactosylceramide; C015831:dimethyldioctadecylammonium; C003460:threitol; D007371:Interferon-gamma; C010942:1,2-distearoyllecithin