title: A liposomal steroid nano-drug for treating systemic lupus erythematosus.
abstract: BACKGROUND
  Glucocorticoids have been known for years to be the most effective therapy in systemic lupus erythematosus. Their use, however, is limited by the need for high doses due to their unfavorable pharmacokinetics and biodistribution. We have previously developed a novel liposome-based steroidal (methylprednisolone hemisuccinate (MPS)) nano-drug and demonstrated its specific accumulation in inflamed tissues, as well as its superior therapeutic efficacy over that of free glucocorticoids (non-liposomal) in the autoimmune diseases, including the adjuvant arthritis rat model and the experimental autoimmune encephalomyelitis mouse model.
  
  
  OBJECTIVE
  In the present work we have evaluated the therapeutic effect of the above liposome-based steroidal (MPS) nano-drug in the MRL-lpr/lpr murine model of SLE and compared it with similar doses of the free MPS.
  
  
  METHODS
  MRL-lpr/lpr mice were treated with daily injections of free MPS or weekly injections of 10% dextrose, empty nano-liposomes or the steroidal nano-drug and the course of their disease was followed up to the age of 24 weeks.
  
  
  RESULTS
  Treatment with the steroidal nano-drug was found to be significantly superior to the free MPS in suppressing anti-dsDNA antibody levels, proliferation of lymphoid tissue and renal damage, and in prolonging survival of animals.
  
  
  CONCLUSIONS
  This significant superiority of our liposome based steroidal nano-drug administered weekly compared with daily injections of free methylprednisolone hemisuccinate in suppressing murine lupus indicates this glucocorticoid nano-drug formulation may be a good candidate for the treatment of human SLE.
authors.affiliation: Department of Medicine-Hadassah University Hospital, Jerusalem, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Moallem
authors.affiliation: The Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Koren
authors.affiliation: Department of Medicine-Hadassah University Hospital, Jerusalem, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Ulmansky
authors.affiliation: Department of Medicine-Hadassah University Hospital, Jerusalem, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Pizov
authors.affiliation: The Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Barlev
authors.affiliation: The Laboratory of Membrane and Liposome Research, Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Barenholz
authors.affiliation: Department of Medicine-Hadassah University Hospital, Jerusalem, Israel yakovn@hadassah.org.il chezyb1@gmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Naparstek
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005260:Female; D008081:Liposomes / Q000008:administration & dosage; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008776:Methylprednisolone Hemisuccinate / Q000008:administration & dosage*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D053758:Nanoparticles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000974:Antibodies, Antinuclear; D008081:Liposomes; D008776:Methylprednisolone Hemisuccinate
keywords: Systemic lupus erythematosus; corticosteroids; treatment