title: Fractional CO(2) laser-assisted drug delivery.
abstract: OBJECTIVE
  Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO(2) laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug.
  
  
  METHODS
  Two Yorkshire swine were treated with single-hole CO(2) laser AFR and subsequent topical application of MAL (Metvix(R), Photocure ASA, Oslo, Norway), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800 microm. AFR was performed with a 10.6 microm wavelength prototype CO(2) laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse.
  
  
  RESULTS
  AFR created cone-shaped channels of approximately 300 microm diameter and 1,850 microm depth that were surrounded by a 70 microm thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P<0.0011) and dermis (P<0.0433) versus MAL alone at skin depths of 120, 500, 1,000, 1,500, and 1,800 microm. AFR before MAL application also enhanced skin surface (epidermal) porphyrin fluorescence. Radial diffusion of MAL from the laser-created channels into surrounding dermis was evidenced by uniform porphyrin fluorescence up to 1,500 microm from the holes (1,000, 1,800 microm depths). Skin massage after MAL application did not affect MAL-induced porphyrin fluorescence after AFR.
  
  
  CONCLUSIONS
  Ablative fractional laser treatment facilitates delivery of topical MAL deeply into the skin. For the conditions of this study, laser channels approximately 3 mm apart followed by MAL application could produce porphyrins throughout essentially the entire skin. AFR appears to be a clinically practical means for enhancing uptake of MAL, a photodynamic therapy drug, and presumably many other topical skin medications.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. mhaedersdal@dadlnet.dk
authors.forename: Merete
authors.initials: M
authors.lastname: Haedersdal
authors.forename: Fernanda H
authors.initials: FH
authors.lastname: Sakamoto
authors.forename: William A
authors.initials: WA
authors.lastname: Farinelli
authors.forename: Apostolos G
authors.initials: AG
authors.lastname: Doukas
authors.forename: Josh
authors.initials: J
authors.lastname: Tam
authors.forename: R Rox
authors.initials: RR
authors.lastname: Anderson
mesh_terms: D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D016503:Drug Delivery Systems; D054020:Lasers, Gas / Q000627:therapeutic use; D028022:Low-Level Light Therapy / Q000379:methods*; D008297:Male; D023421:Models, Animal; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D012869:Skin Absorption / Q000187:drug effects / Q000528:radiation effects; D013552:Swine
chemical_list: D017319:Photosensitizing Agents; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid