title: Therapeutic effect of methotrexate encapsulated in cationic liposomes (EndoMTX) in comparison to free methotrexate in an antigen-induced arthritis study in vivo.
abstract: OBJECTIVE
  Cationic lipid complexes bind to angiogenic endothelial cells of solid tumours and microvessels of chronic inflammatory tissue. Methotrexate (MTX) is one of the drugs used in the therapy of rheumatoid arthritis (RA); it is applied systemically but can have serious side-effects. The aim of this study was to investigate the impact of MTX encapsulated in cationic liposomes (EndoMTX) in comparison to treatment with free MTX.
  
  
  METHODS
  We used an antigen-induced arthritis (AiA) model and investigated the leucocyte- and platelet-endothelial cell interaction in arthritic female C57/Bl6 mice and in healthy controls. The arthritic animals were divided into four different groups receiving either trehalose, free MTX, EndoMTX placebo, or EndoMTX. These parameters and functional capillary density (FCD) were measured and assessed by intravital microscopy (IVM). We controlled clinical parameters such as the knee joint diameter (KJD) throughout the observation period.
  
  
  RESULTS
  Animals treated with EndoMTX showed a significant and superior reduction in leucocyte- and platelet-endothelial cell interaction, FCD, and KJD. Free MTX or empty liposomes also showed a reduction in these parameters but not to a significant level. FCD decreased in the EndoMTX group in comparison to using free drugs or empty carrier-like liposomes.
  
  
  CONCLUSIONS
  This study demonstrates the advantage of using MTX encapsulated in cationic liposomes in contrast to free and generic MTX, with a higher efficacy in anti-inflammatory and anti-angiogenic abilities. Targeting with cationic liposomes may be a promising treatment option and should be elucidated in further experiments regarding dose reduction and side-effects due to MTX usage.
authors.affiliation: a Department of Trauma and Reconstructive Surgery , Ludwig Maximilians University Munich , Germany.|b Walter Brendel Centre of Experimental Medicine , Ludwig Maximilians University Munich , Germany.
authors.forename: O
authors.initials: O
authors.lastname: Gottschalk
authors.affiliation: a Department of Trauma and Reconstructive Surgery , Ludwig Maximilians University Munich , Germany.|b Walter Brendel Centre of Experimental Medicine , Ludwig Maximilians University Munich , Germany.
authors.forename: P
authors.initials: P
authors.lastname: Metz
authors.affiliation: b Walter Brendel Centre of Experimental Medicine , Ludwig Maximilians University Munich , Germany.
authors.forename: M L
authors.initials: ML
authors.lastname: Dao Trong
authors.affiliation: c Schön Klinik, Munich Harlaching , Ludwig Maximilians University Munich , Germany.
authors.forename: S
authors.initials: S
authors.lastname: Altenberger
authors.affiliation: d Department of Orthopaedic Surgery , Ludwig Maximilians University Munich , Germany.
authors.forename: V
authors.initials: V
authors.lastname: Jansson
authors.affiliation: a Department of Trauma and Reconstructive Surgery , Ludwig Maximilians University Munich , Germany.
authors.forename: W
authors.initials: W
authors.lastname: Mutschler
authors.affiliation: b Walter Brendel Centre of Experimental Medicine , Ludwig Maximilians University Munich , Germany.|d Department of Orthopaedic Surgery , Ludwig Maximilians University Munich , Germany.|e Medical Park Chiemsee , Bernau am Chiemsee , Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmitt-Sody
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000942:Antigens, Bacterial / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D001792:Blood Platelets / Q000473:pathology; D002214:Capsules; D002450:Cell Communication / Q000502:physiology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D007719:Knee Joint / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D008081:Liposomes; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology; D011859:Radiography; D016896:Treatment Outcome
chemical_list: D000942:Antigens, Bacterial; D018501:Antirheumatic Agents; D002214:Capsules; D008081:Liposomes; D008727:Methotrexate