title: A novel liposomal formulation of FTY720 (fingolimod) for promising enhanced targeted delivery.
abstract: We describe here the development and characterization of the physicochemical and pharmacokinetic properties of a novel liposomal formulation for FTY720 delivery, LP-FTY720. The mean diameter of LP-FTY720 was ~157 nm, and the FTY720 entrapment efficiency was ~85%. The liposomal formulation protected FTY720 from degradation in aqueous buffer and showed toxicity in CLL patient B cells comparable to that of free FTY720. Following intravenous injection in ICR mice, LP-FTY720 had an increased elimination phase half-life (~28 vs. ~19 hr) and decreased clearance (235 vs. 778 mL/h/kg) compared to the free drug. Antibodies against CD19, CD20 and CD37 were incorporated into LP-FTY720, which provided targeted delivery to CLL patient B cells and thus achieved higher killing efficacy. The novel liposomal carrier of FTY720 demonstrated improved pharmacokinetic properties, comparable activity, and a potential platform for targeted delivery to CLL by overcoming the limited application of free FTY720 to B malignancy treatment.
  
  
  BACKGROUND
  This team reports on a novel liposomal formulation for FTY720 delivery, demonstrating improved pharmacokinetic properties, comparable activity, and a potential platform for targeted delivery to CLL using antibodies incorporated in the liposomes. The method expected to overcome the limited application of free FTY720 to B malignancy treatment.
authors: Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH, USA; Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors: Yicheng
authors: Y
authors: Mao
authors: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors: Jiang
authors: J
authors: Wang
authors: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors: Yuan
authors: Y
authors: Zhao
authors: Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH, USA; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
authors: Yun
authors: Y
authors: Wu
authors: Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH, USA; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
authors: Kwang Joo
authors: KJ
authors: Kwak
authors: Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, Columbus, OH, USA.
authors: Ching-Shih
authors: CS
authors: Chen
authors: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors: John C
authors: JC
authors: Byrd
authors: Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH, USA; Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors: Robert J
authors: RJ
authors: Lee
authors: Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors: Mitch A
authors: MA
authors: Phelps
authors: Center for Affordable Nanoengineering of Polymeric Biomedical Devices (CANPBD), The Ohio State University, Columbus, OH, USA; William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
authors: L James
authors: LJ
authors: Lee
authors: Division of Hematology and Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA. Electronic address: raj.muthusamy@osumc.edu.
authors: Natarajan
authors: N
authors: Muthusamy
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D018951:Antigens, CD20 / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D050997:Nanomedicine; D011409:Propylene Glycols / Q000737:chemistry*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry; D059470:Tetraspanins / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D018941:Antigens, CD19; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; C059071:CD37 protein, human; D008081:Liposomes; D011409:Propylene Glycols; D059470:Tetraspanins; D014867:Water; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
keywords: CD37; Drug delivery; FTY720; Leukemia; Liposome; Nanotechnology
references: Clin Cancer Res. 2013 Jan 15;19(2):347-56
references: 23209030
references: Cancer Cell. 2012 May 15;21(5):694-708
references: 22624718
references: Drug Metab Dispos. 2006 Sep;34(9):1480-7
references: 16751263
references: Clin Cancer Res. 2002 Apr;8(4):1172-81
references: 11948130
references: BioDrugs. 2001;15(4):215-24
references: 11437687
references: Blood. 2011 Sep 8;118(10):2793-800
references: 21768294
references: Nat Rev Drug Discov. 2008 Sep;7(9):771-82
references: 18758474
references: Blood. 2007 Oct 1;110(7):2569-77
references: 17440052
references: Biomaterials. 2013 Aug;34(26):6185-93
references: 23726226
references: Br J Pharmacol. 2002 Dec;137(7):953-62
references: 12429567
references: Biochim Biophys Acta. 1995 Nov 1;1239(2):133-44
references: 7488618
references: Breast Cancer Res. 2002;4(3):95-9
references: 12052251
references: Leukemia. 2012 Jul;26(7):1720-2
references: 22333878
references: Blood. 2008 Jan 1;111(1):275-84
references: 17761520
references: Blood. 2013 Jan 3;121(1):136-47
references: 23165478
references: J Mol Cell Cardiol. 2010 Feb;48(2):406-14
references: 19852968
references: Transplantation. 1996 Jan 27;61(2):200-5
references: 8600623
references: Biomaterials. 2012 Nov;33(32):8131-41
references: 22858002
references: J Immunol. 2007 Feb 15;178(4):2458-68
references: 17277153
references: Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1487-95
references: 21705677
references: Nat Rev Drug Discov. 2010 Nov;9(11):883-97
references: 21031003
references: Ann Oncol. 2000 Aug;11(8):1029-33
references: 11038041
references: Br J Pharmacol. 2003 Apr;138(7):1303-12
references: 12711631
references: Transplantation. 2003 Oct 15;76(7):1079-84
references: 14557756
references: J Colloid Interface Sci. 2003 May 15;261(2):402-10
references: 16256549
references: Cancer Res. 2008 Feb 15;68(4):1204-12
references: 18281497
references: Pharmacol Ther. 2007 Jul;115(1):84-105
references: 17561264
references: Blood. 2011 Dec 22;118(26):6893-903
references: 22042694
references: J Immunol. 2011 Oct 15;187(8):4310-8
references: 21918186
references: Clin Pharmacokinet. 2012 Jan 1;51(1):15-28
references: 22149256
references: Int J Pharm. 2007 Oct 1;343(1-2):255-61
references: 17624698
references: J Clin Apher. 2003;18(3):141-52
references: 14569608
references: Cancer Res. 2006 Jul 1;66(13):6732-40
references: 16818648
references: Blood. 2010 Feb 11;115(6):1204-13
references: 19965644
references: Blood. 2010 Oct 7;116(14):2554-8
references: 20574049
references: Hepatology. 2011 Jun;53(6):1943-58
references: 21391227
references: Immunopharmacology. 2000 Jun;48(1):75-85
references: 10822091
references: J Nat Prod. 2011 Apr 25;74(4):900-7
references: 21456524
references: J Clin Pharmacol. 2005 Nov;45(11):1268-78
references: 16239360
references: Clin Cancer Res. 2010 Jun 15;16(12):3182-92
references: 20460491
references: Semin Oncol. 2004 Dec;31(6 Suppl 13):196-205
references: 15717745
references: J Clin Invest. 2007 Sep;117(9):2408-21
references: 17717597
references: Int J Pharm. 2009 Jan 5;365(1-2):170-4
references: 18778761