title: Lack of effect of selected sunscreens applied on ex vivo human skin for 5-methyl-aminolevulinic acid penetration and protoporphyrin IX photoactivation.
abstract: BACKGROUND
  Photodynamic therapy (PDT) is a successful treatment for non-melanoma skin cancers. Methyl-aminolevulinate (MAL) is metabolized to protoporphyrin IX (PpIX) which accumulates in the skin lesion and which generates a painful photochemical toxic reaction upon red light exposure. PDT using daylight (DL) exposure is now used to reduce pain and subjects are advised to protect the areas with sunscreen. This work investigated the effect of sunscreen on MAL penetration and PpIX photoactivation in ex vivo human skin.
  
  
  METHODS
  To measure skin penetration of MAL, particle-free sunscreens were applied on ex vivo human skin samples mounted on diffusion cells before application of Metvix cream containing [14C]-MAL for 2.5h. To circumvent the absence of skin penetration of PpIX, skin samples were first treated with microneedles and mounted on diffusion cells before the application of PpIX solution for 1h followed by sunscreens. Skin samples were then exposed to solar simulator for 1h. Concentrations of [14C]-MAL or PpIX were measured in both total skin and receptor liquid.
  
  
  CONCLUSIONS
  The results showed that the in vitro skin penetration of MAL and the PpIX photoactivation on ex vivo human skin samples are not modified by pretreatments of ex vivo human skin with sunscreens. This study demonstrates that neither in vitro skin penetration of MAL nor PpIX photoactivation were modified by pretreatments with Cetaphil SPF 30 Dermacontrol and Actinica®Lotion SPF 50+. This supports the efficacy and safety of MAL DL-PDT in the clinical situation.
authors.affiliation: Galderma R&D, Les Templiers, Route des Colles BP 87, F-06902 Sophia-Antipolis, France. Electronic address: hanan.osman-ponchet@galderma.com.
authors.forename: Hanan
authors.initials: H
authors.lastname: Osman-Ponchet
authors.affiliation: Galderma R&D, Les Templiers, Route des Colles BP 87, F-06902 Sophia-Antipolis, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Sevin
authors.affiliation: Galderma R&D, Les Templiers, Route des Colles BP 87, F-06902 Sophia-Antipolis, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gaborit
authors.affiliation: Galderma R&D, Les Templiers, Route des Colles BP 87, F-06902 Sophia-Antipolis, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Kouidhi
authors.affiliation: Galderma R&D, Les Templiers, Route des Colles BP 87, F-06902 Sophia-Antipolis, France.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hanaizi
authors.affiliation: Galderma R&D, Les Templiers, Route des Colles BP 87, F-06902 Sophia-Antipolis, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Comby
authors.affiliation: Galderma R&D, Les Templiers, Route des Colles BP 87, F-06902 Sophia-Antipolis, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Ruty
authors.affiliation: Galderma R&D, Les Templiers, Route des Colles BP 87, F-06902 Sophia-Antipolis, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Bouvier
mesh_terms: D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011524:Protoporphyrins / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D013473:Sunscreening Agents / Q000494:pharmacology*
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D013473:Sunscreening Agents; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: Methyl aminolevulinate; Photodynamic therapy; PpIX photoactivation; Skin penetration; Sunscreen