title: Liposomal tacrolimus lotion as a novel topical agent for treatment of immune-mediated skin disorders: experimental studies in a murine model.
abstract: BACKGROUND
  Systemic but not topical tacrolimus (TAC) is effective against psoriasis. Mechanical methods that enhance skin penetration by TAC increase its topical antipsoriatic effect. Liposomal delivery of TAC would increase its penetration of skin, allow for slow release and diminish its toxicity.
  
  
  OBJECTIVE
  To test a liposomal TAC (LTAC) formulation in a murine model.
  
  
  METHODS
  Drug penetration was assessed using radiolabelled LTAC, and the effect of TAC and LTAC on Balb/c skin graft survival and on ovalbumin-induced delayed-type hypersensitivity reactions was tested in C57BL/6 mice.
  
  
  RESULTS
  Radiotracer studies showed that topical application of LTAC achieved nine times the concentration of TAC at a target site than did systemic administration of TAC. Combination of systemic and topical LTAC significantly increased mean +/- SD skin graft survival (14.8 +/- 1.5 days) compared with systemic TAC (8.0 +/- 0.7 days) and control mice (8.4 +/- 1.2 days). LTAC was more effective systemically than TAC in the prevention of delayed-type hypersensitivity reactions. Topical LTAC also prevented this response.
  
  
  CONCLUSIONS
  Topical LTAC was effective in this model of immune-mediated skin disease. Because LTAC achieves higher skin concentrations than systemic TAC it may be an effective delivery system for TAC in the treatment of psoriasis.
authors.affiliation: Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Erdogan
authors.forename: J R
authors.initials: JR
authors.lastname: Wright
authors.forename: V C
authors.initials: VC
authors.lastname: McAlister
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D006085:Graft Survival / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010047:Ovalbumin / Q000009:adverse effects; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D007166:Immunosuppressive Agents; D008081:Liposomes; D010047:Ovalbumin; D016559:Tacrolimus