title: Fractional laser-assisted delivery of methyl aminolevulinate: Impact of laser channel depth and incubation time.
abstract: OBJECTIVE
  Pretreatment of skin with ablative fractional lasers (AFXL) enhances the uptake of topical photosensitizers used in photodynamic therapy (PDT). Distribution of photosensitizer into skin layers may depend on depth of laser channels and incubation time. This study evaluates whether depth of intradermal laser channels and incubation time may affect AFXL-assisted delivery of methyl aminolevulinate (MAL).
  
  
  METHODS
  Yorkshire swine were treated with CO2 AFXL at energy levels of 37, 190, and 380 mJ/laser channel and subsequent application of MAL cream (Metvix) for 30, 60, 120, and 180 minutes incubation time. Fluorescence photography and fluorescence microscopy quantified MAL-induced porphyrin fluorescence (PpIX) at the skin surface and at five specific skin depths (120, 500, 1,000, 1,500, and 1,800 µm).
  
  
  RESULTS
  Laser channels penetrated into superficial (∼300 µm), mid (∼1,400 µm), and deep dermis/upper subcutaneous fat layer (∼2,100 µm). Similar fluorescence intensities were induced at the skin surface and throughout skin layers independent of laser channel depth (180 minutes; P < 0.19). AFXL accelerated PpIX fluorescence from skin surface to deep dermis. After laser exposure and 60 minutes MAL incubation, surface fluorescence was significantly higher compared to intact, not laser-exposed skin at 180 minutes (AFXL-MAL 60 minutes vs. MAL 180 minutes, 69.16 a.u. vs. 23.49 a.u.; P < 0.01). Through all skin layers (120-1,800 µm), laser exposure and 120 minutes MAL incubation induced significantly higher fluorescence intensities in HF and dermis than non-laser exposed sites at 180 minutes (1,800 µm, AFXL-MAL 120 minutes vs. MAL 180 minutes, HF 14.76 a.u. vs. 6.69 a.u. and dermis 6.98 a.u. vs. 5.87 a.u.; P < 0.01).
  
  
  CONCLUSIONS
  AFXL pretreatment accelerates PpIX accumulation, but intradermal depth of laser channels does not affect porphyrin accumulation. Further studies are required to examine these findings in clinical trials.
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark. christinahaak@dadlnet.dk
authors.forename: Christina S
authors.initials: CS
authors.lastname: Haak
authors.forename: William A
authors.initials: WA
authors.lastname: Farinelli
authors.forename: Joshua
authors.initials: J
authors.lastname: Tam
authors.forename: Apostolos G
authors.initials: AG
authors.lastname: Doukas
authors.forename: R Rox
authors.initials: RR
authors.lastname: Anderson
authors.forename: Merete
authors.initials: M
authors.lastname: Haedersdal
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D016503:Drug Delivery Systems; D005260:Female; D005453:Fluorescence; D054020:Lasers, Gas; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011166:Porphyrins; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D034421:Sus scrofa; D013997:Time Factors
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid