title: Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment.
abstract: OBJECTIVE
  Photodynamic therapy (PDT) of thick skin lesions is limited by topical drug uptake. Ablative fractional resurfacing (AFR) creates vertical channels that may facilitate topical PDT drug penetration and improve PDT-response in deep skin layers. The purpose of this study was to evaluate whether pre-treating the skin with AFR before topically applied methyl aminolevulinate (MAL) could enable a deep PDT-response.
  
  
  METHODS
  Yorkshire swine were treated under general anesthesia with a fractional CO(2) laser using stacked single pulses of 3 milliseconds, 91.6 mJ per pulse and subsequent topical MAL application for 3 hours (Metvix®). Red light (LED arrays) was then delivered at fluences of 37 and 200 J/cm(2). Fluorescent photography and microscopy was used to quantify MAL-induced porphyrin distribution and PDT-induced photobleaching at the skin surface and five specific depths down to 1,800 µm.
  
  
  RESULTS
  Laser-ablated channels were approximately 1,850 µm deep, which significantly increased topical MAL-induced porphyrin fluorescence (hair follicles, dermis, P < 0.0001) and PDT response, both superficially and deep, versus topical MAL application alone. The fraction of porphyrin fluorescence lost by photobleaching was slightly less after 37 J/cm(2) than after 200 J/cm(2) (overall median values 67-90%; 37 vs. 200 J/cm(2), P > 0.05 for all but one comparison). Photobleaching was steady throughout skin layers and did not vary significantly with skin depth at either LED fluence (P > 0.05).
  
  
  CONCLUSIONS
  AFR greatly facilitates topical MAL-induced porphyrins and the fraction of photobleached porphyrins is similar for superficial and deep skin. These observations are consistent with AFR-enhanced uptake of MAL, increased porphyrin synthesis, and photodynamic activation of deep porphyrins even at the lower fluence of 37 J/cm(2), widely used in clinical practice. AFR appears to be a clinically practical means for improving PDT deep into the skin. Clinical studies are suggested to evaluate selectivity in targeting dysplastic cell types.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. mhaedersdal@dadlnet.dk
authors.forename: M
authors.initials: M
authors.lastname: Haedersdal
authors.forename: J
authors.initials: J
authors.lastname: Katsnelson
authors.forename: F H
authors.initials: FH
authors.lastname: Sakamoto
authors.forename: W A
authors.initials: WA
authors.lastname: Farinelli
authors.forename: A G
authors.initials: AG
authors.lastname: Doukas
authors.forename: J
authors.initials: J
authors.lastname: Tam
authors.forename: R R
authors.initials: RR
authors.lastname: Anderson
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D003131:Combined Modality Therapy; D054020:Lasers, Gas; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects; D034421:Sus scrofa
chemical_list: D017319:Photosensitizing Agents; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid