title: Topical formulations of miltefosine for cutaneous leishmaniasis in a BALB/c mouse model.
abstract: Cutaneous leishmaniasis (CL) is caused by several species of the protozoan parasite Leishmania and affects approximately 10 million people worldwide. Currently available drugs are not ideal due to high cost, toxicity, parenteral administration and suboptimal efficacy. Miltefosine is the only oral treatment (Impavido®) available to treat CL, given over a period of 28 days with common side effects such as vomiting and diarrhoea.
  
  
  OBJECTIVE
  To explore the local application of miltefosine as a topical formulation to enhance activity and reduce the drug's adverse effects.
  
  
  METHODS
  The antileishmanial activity of miltefosine was confirmed in vitro against several Leishmania species. The permeation of miltefosine, in different solvents and solvent combinations, through BALB/c mouse skin was evaluated in vitro using Franz diffusion cells. The topical formulations which enabled the highest drug permeation or skin disposition were tested in vivo in BALB/c mice infected with L. major.
  
  
  RESULTS
  The overall permeation of miltefosine through skin was low regardless of the solvents used. This was reflected in limited antileishmanial activity of the drug formulations when applied topically in vivo. All topical formulations caused skin irritation.
  
  
  CONCLUSIONS
  We conclude that miltefosine is not an appropriate candidate for the topical treatment of CL.
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, London, UK.|Department of Infection and Immunology, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Katrien
authors.initials: K
authors.lastname: Van Bocxlaer
authors.affiliation: Department of Infection and Immunology, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Yardley
authors.affiliation: Department of Pharmaceutics, UCL School of Pharmacy, London, UK.
authors.forename: Sudaxshina
authors.initials: S
authors.lastname: Murdan
authors.affiliation: Department of Infection and Immunology, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Simon L
authors.initials: SL
authors.lastname: Croft
mesh_terms: D000287:Administration, Topical; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004339:Drug Compounding; D005260:Female; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D051379:Mice; D021261:Parasitic Sensitivity Tests; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012869:Skin Absorption; D012995:Solubility; D012997:Solvents
chemical_list: D012997:Solvents; D010767:Phosphorylcholine; C039128:miltefosine
keywords: cutaneous leishmaniasis; drug delivery; miltefosine; skin; topical formulation