title: Percutaneous penetration characteristics and release kinetics of contact allergens encapsulated in ethosomes.
abstract: BACKGROUND
  Formulation of the contact allergens dinitrochlorobenzene and isoeugenol in ethanolic liposomes (ethosomes) increases their sensitizing properties in the local lymph node assay compared with an ethanol-water formulation of the allergens. Likewise, isoeugenol and methyldibromo-glutaronitrile formulated in ethosomes enhanced the patch test reactions in sensitized human volunteers. The relationship between the percutaneous penetration/absorption and sensitization/elicitation phases of contact allergy is not well elucidated.
  
  
  OBJECTIVE
  The aim of this study was to investigate whether the observed increased sensitizing and elicitation properties following the formulation of selected contact allergens in ethosomes could be explained by a change in release kinetics of the allergens and their pattern of percutaneous penetration and absorption as well as allergen deposition in epidermis and dermis.
  
  
  METHODS
  Release kinetics were studied using dialysis bags, and samples were taken at selected time points until equilibrium was reached. Percutaneous absorption and penetration were studied using human skin on Franz cells, and receptor fluid samples were taken at selected time points. Experiments were terminated after 24 hours, and deposition of allergen in epidermis and dermis was measured. Maximum flux and lag time were calculated.
  
  
  RESULTS
  Ethosome formulation decreased the release of both allergens compared with the ethanol-water formulation. Ethosome formulation of dinitrochlorobenzene increased its percutaneous penetration but reduced the percutaneous penetration of isoeugenol compared with control formulations. Likewise, all other calculated parameters showed an opposite trend for the 2 allergens in ethosomes and ethanol-water.
  
  
  CONCLUSIONS
  The present study demonstrates that identical ethosomes affect the percutaneous penetration characteristics of 2 allergens differently. Thus, our results indicate that each combination of an allergen and a vehicle needs to be evaluated separately. The exact mechanistic relationship between percutaneous penetration, release kinetics, and allergenicity of chemicals in various vehicles remains to be clarified.
authors.affiliation: Department of Dermatology, Odense University Hospital, University of Southern Denmark, Odense, Denmark. jtm@dadlnet.dk
authors.forename: Jakob Torp
authors.initials: JT
authors.lastname: Madsen
authors.forename: Stefan
authors.initials: S
authors.lastname: Vogel
authors.forename: Jeanne Duus
authors.initials: JD
authors.lastname: Johansen
authors.forename: Jens Ahm
authors.initials: JA
authors.lastname: Sørensen
authors.forename: Klaus Ejner
authors.initials: KE
authors.lastname: Andersen
authors.forename: Jesper Bo
authors.initials: JB
authors.lastname: Nielsen
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D017449:Dermatitis, Allergic Contact; D004137:Dinitrochlorobenzene / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D005054:Eugenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007114:Immunization; D007509:Irritants / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption
chemical_list: D000485:Allergens; D004137:Dinitrochlorobenzene; D007509:Irritants; D008081:Liposomes; D000431:Ethanol; D005054:Eugenol; C036643:isoeugenol