PMID- 21283989 OWN - NLM STAT- MEDLINE DCOM- 20110912 LR - 20231115 IS - 1520-6017 (Electronic) IS - 0022-3549 (Print) IS - 0022-3549 (Linking) VI - 100 IP - 7 DP - 2011 Jul TI - Preparation, characterisation and entrapment of a non-glycosidic threitol ceramide into liposomes for presentation to invariant natural killer T cells. PG - 2724-33 LID - 10.1002/jps.22500 [doi] 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 alpha-galactosylceramide, which stimulates the production of large quantities of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). However, alphaGalCer leads to overstimulation of iNKT cells. It has been demonstrated that the alphaGalCer 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-gamma 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. CI - Copyright (c) 2011 Wiley-Liss, Inc. and the American Pharmacists Association FAU - Kaur, Randip AU - Kaur R AD - School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK. FAU - Chen, Jili AU - Chen J FAU - Dawoodji, Amina AU - Dawoodji A FAU - Cerundolo, Vincenzo AU - Cerundolo V FAU - Garcia-Diaz, Yoel R AU - Garcia-Diaz YR FAU - Wojno, Justyna AU - Wojno J FAU - Cox, Liam R AU - Cox LR FAU - Besra, Gurdyal S AU - Besra GS FAU - Moghaddam, Behfar AU - Moghaddam B FAU - Perrie, Yvonne AU - Perrie Y LA - eng GR - G0400421/MRC_/Medical Research Council/United Kingdom GR - G1000800/MRC_/Medical Research Council/United Kingdom GR - 084923/WT_/Wellcome Trust/United Kingdom GR - 11331/CRUK_/Cancer Research UK/United Kingdom GR - 084923/B/08/7/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110131 PL - United States TA - J Pharm Sci JT - Journal of pharmaceutical sciences JID - 2985195R RN - 0 (Adjuvants, Immunologic) RN - 0 (Galactosylceramides) RN - 0 (Liposomes) RN - 0 (Phosphatidylcholines) RN - 0 (Quaternary Ammonium Compounds) RN - 0 (Sugar Alcohols) RN - 0 (alpha-galactosylceramide) RN - 251IW5I21C (dimethyldioctadecylammonium) RN - 6DN82XBT5M (threitol) RN - 82115-62-6 (Interferon-gamma) RN - EAG959U971 (1,2-distearoyllecithin) SB - IM MH - Adjuvants, Immunologic/administration & dosage/chemistry/*pharmacology MH - Cells, Cultured MH - Chemistry, Pharmaceutical MH - Dendritic Cells/*drug effects/immunology MH - Drug Compounding MH - Drug Stability MH - Galactosylceramides/administration & dosage/chemistry/*pharmacology MH - Humans MH - Interferon-gamma/metabolism MH - Killer Cells, Natural/*drug effects/immunology MH - Kinetics MH - Liposomes MH - Particle Size MH - Phosphatidylcholines/*chemistry MH - Quaternary Ammonium Compounds/*chemistry MH - Solubility MH - Sugar Alcohols/administration & dosage/chemistry/*pharmacology MH - Technology, Pharmaceutical/methods PMC - PMC3818697 MID - EMS55480 OID - NLM: EMS55480 EDAT- 2011/02/02 06:00 MHDA- 2011/09/13 06:00 PMCR- 2013/11/06 CRDT- 2011/02/02 06:00 PHST- 2010/11/12 00:00 [received] PHST- 2010/12/13 00:00 [revised] PHST- 2010/12/14 00:00 [accepted] PHST- 2011/02/02 06:00 [entrez] PHST- 2011/02/02 06:00 [pubmed] PHST- 2011/09/13 06:00 [medline] PHST- 2013/11/06 00:00 [pmc-release] AID - S0022-3549(15)32063-3 [pii] AID - 10.1002/jps.22500 [doi] PST - ppublish SO - J Pharm Sci. 2011 Jul;100(7):2724-33. doi: 10.1002/jps.22500. Epub 2011 Jan 31.