title: Epidermal penetration and protoporphyrin IX formation of two different 5-aminolevulinic acid formulations in ex vivo human skin.
abstract: BACKGROUND
  Photosensitizer formation and epidermal penetration depth represent basic predictors of drug efficacy in dermatological Photodynamic Therapy (PDT). Different drug formulations and application standards are used to perform PDT in clinical practice.
  
  
  METHODS
  Thus, we developed a human ex vivo model suitable to explore drug permeation in human skin and compared in 10 patients the penetration of nanoemulsion formulation (BF-200 ALA) with that of a 20% ALA cream formulation frequently used in clinical practice. Protoporphyrin IX (PpIX) formation was assessed according to different durations of incubation with both preparations.
  
  
  RESULTS
  BF-200 ALA led to more intense PpIX fluorescence than the 20% ALA cream formulation as assessed by fluorescence microscopy: after 12h of incubation, total measured fluorescence was at 101,995 fluorescence units with BF-200 ALA and 40,960 fluorescence units with 20% ALA cream, respectively. This could be reproduced using quantitative fluorimetric measurements in tissue lysates. After the clinically relevant incubation time of 3h the PpIX concentration induced by BF-200 ALA was more than three-fold higher than that induced by the 20% ALA formulation (7.1±5.5 and 1.9±1.8nmol/l, p<0.05, Mann-Whitney U-test) and four-fold higher after 12h (30.0±4.6 and 6.7±2.0nmol/l, p<0.01, Mann-Whitney U-test).
  
  
  CONCLUSIONS
  In spite of the 50% lower ALA content BF-200 ALA triggers significantly higher PpIX concentrations than the 20% ALA formulation, indicating that clinical efficacy with BF-200 ALA may be higher. Moreover, the ex vivo eyelid skin model may represent a useful tool to investigate drug permeation in human skin.
authors.affiliation: Department of Dermatology, Ruhr-University, Bochum, Germany; CentroDerm GmbH, Heinz-Fangman-Straße 57, Wuppertal, Germany. Electronic address: l.schmitz@klinikum-bochum.de.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schmitz
authors.affiliation: Department of Animal Physiology, Ruhr-University, Universitätsstraße 150, Bochum, Germany.
authors.forename: Ben
authors.initials: B
authors.lastname: Novak
authors.affiliation: Department of Animal Physiology, Ruhr-University, Universitätsstraße 150, Bochum, Germany.
authors.forename: Ann-Kathrin
authors.initials: AK
authors.lastname: Hoeh
authors.affiliation: Department of Animal Physiology, Ruhr-University, Universitätsstraße 150, Bochum, Germany.
authors.forename: Herman
authors.initials: H
authors.lastname: Luebbert
authors.affiliation: CentroDerm GmbH, Heinz-Fangman-Straße 57, Wuppertal, Germany; Faculty of Health, University Witten-Herdecke, Alfred-Herrhausen-Straße 50, Witten, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dirschka
mesh_terms: D000328:Adult; D000622:Aminolevulinic Acid / Q000145:classification* / Q000627:therapeutic use; D004817:Epidermis / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D011524:Protoporphyrins / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: 5-Aminolevulinic acid; BF-200 ALA; Nanoemulsion; Organotypic skin culture; Photodynamic Therapy; Protoporphyrin IX