title: Ablative fractional laser enhances MAL-induced PpIX accumulation: Impact of laser channel density, incubation time and drug concentration.
abstract: OBJECTIVE
  Pretreatment of skin with ablative fractional laser enhances accumulation of topical provided photosensitizer, but essential information is lacking on the interaction between laser channel densities and pharmacokinetics. Hence our objectives were to investigate how protoporphyrin accumulation was affected by laser densities, incubation time and drug concentration.
  
  
  METHODS
  We conducted the study on the back of healthy male volunteers (n=11). Test areas were pretreated with 2940nm ablative fractional Er:YAG laser, 11.2mJ per laser channel using densities of 1, 2, 5, 10 and 15% (AFL 1-15%). Control areas received pretreatment with curettage or no pretreatment. Methyl aminolevulinate (MAL) was applied under occlusion in concentrations of 0, 80 and 160mg/g. MAL-induced protoporphyrin fluorescence was quantified with a handheld photometer after 0, 30, 60, 120 and 180min incubation. The individual fluorescence intensity reached from the highest density (15%) and longest MAL 160mg/g incubation time (180min) was selected as reference (100%) for other interventional measurements.
  
  
  RESULTS
  A low laser density of 1% markedly enhanced fluorescence intensities from 34% to 75% (no pretreatment vs. AFL 1%, MAL 160mg/g, 180min; p<0.001). Furthermore, fluorescence intensities increased substantially by enhancing densities up to 5% (p≤0.0195). Accumulation of protoporphyrins was accelerated by laser exposure. Thus, laser exposure of 5% density and a median incubation time of 80min MAL (range 46-133min) induced fluorescence levels similar to curettage and 180min incubation. Furthermore, MAL 80 and 160mg/g induced similar fluorescence intensities in skin exposed to laser densities of 1, 2 and 5% (p>0.0537, 30-180min).
  
  
  CONCLUSIONS
  MAL-induced protoporphyrin accumulation is augmented by enhancing AFL densities up to 5%. Further, this model indicates that incubation time as well as drug concentration of MAL may be reduced with laser pretreatment.
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark. Electronic address: christinahaak@dadlnet.dk.
authors.forename: C S
authors.initials: CS
authors.lastname: Haak
authors.affiliation: Dia-Medico ApS, Copenhagen, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Christiansen
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A M
authors.initials: AM
authors.lastname: Erlendsson
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: E H
authors.initials: EH
authors.lastname: Taudorf
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: D
authors.initials: D
authors.lastname: Thaysen-Petersen
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: H C
authors.initials: HC
authors.lastname: Wulf
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Haedersdal
mesh_terms: D000293:Adolescent; D000328:Adult; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007834:Lasers; D008297:Male; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000378:metabolism; D011524:Protoporphyrins / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D055815:Young Adult
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX
keywords: Drug delivery; Fractional Er:YAG laser; Methyl aminolevulinate; Photosensitizer