title: Liposomal codelivery of a synergistic combination of bioactive lipids in the treatment of acute myeloid leukemia.
abstract: OBJECTIVE
  The aim of this work was to develop a liposomal formulation to facilitate delivery of a synergistic safingol/C2-ceramide combination in the treatment of acute myeloid leukemia (AML).
  
  
  METHODS
  Liposomes were prepared using the extrusion method and the bioactive lipids were encapsulated passively. Drug concentrations were determined by liquid chromatography tandem mass spectrometry. Antileukemic activity was evaluated using human leukemic cell lines, patient samples and U937 leukemic xenograft models.
  
  
  RESULTS
  A stable liposome formulation was developed to coencapsulate safingol and C2-ceramide at 1:1 molar ratio with >90% encapsulation efficiency. The liposomal safingol/C2-ceramide was effective in AML cell lines, patient samples and murine xenograft models of AML, compared with liposomal safingol or liposomal C2-ceramide alone despite a dose reduction of 33%.
  
  
  CONCLUSIONS
  Our study provided proof-of-concept evidence to deliver synergistic combination of bioactive lipid to achieve complete remission in AML.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 02-09, 18 Science Drive 4, Singapore 117543, Singapore.
authors.forename: Kuan-Boone
authors.initials: KB
authors.lastname: Tan
authors.forename: Leong-Uung
authors.initials: LU
authors.lastname: Ling
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Bunte
authors.forename: Wee-Joo
authors.initials: WJ
authors.lastname: Chng
authors.forename: Gigi N C
authors.initials: GN
authors.lastname: Chiu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D049109:Cell Proliferation; D002470:Cell Survival; D002518:Ceramides / Q000737:chemistry; D002784:Cholesterol / Q000737:chemistry; D002853:Chromatography, Liquid; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010713:Phosphatidylcholines / Q000737:chemistry; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; D008055:Lipids; D008081:Liposomes; C064769:N-acetylsphingosine; D010713:Phosphatidylcholines; D002784:Cholesterol; C010942:1,2-distearoyllecithin; D013110:Sphingosine; C005682:safingol
keywords: C2-ceramide; U937; acute myeloid leukemia; hemolysis; liposome; safingol; sever combined immunodeficiency mouse; sphingolipid; synergistic combination; zeta-potential