Fractional CO(2) laser-assisted drug delivery

Merete Haedersdal, Fernanda H Sakamoto, William A Farinelli, Apostolos G Doukas, Josh Tam, R Rox Anderson

206 Citations (Scopus)

Abstract

Background and Objectives: 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 CO2 laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug. Materials and Methods: Two Yorkshire swine were treated with single-hole CO2 laser AFR and subsequent topical application of MAL (Metvix®, 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 μm. AFR was performed with a 10.6 μmwavelength prototype CO2 laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse. Results: AFR created cone-shaped channels of approximately 300 μm diameter and 1,850 μm depth that were surrounded by a 70 μm 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 μm. 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 μm from the holes (1,000, 1,800 μmdepths). 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 3mm 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.

Original languageEnglish
JournalLasers in Surgery and Medicine
Volume42
Issue number2
Pages (from-to)113-22
Number of pages10
ISSN0196-8092
DOIs
Publication statusPublished - 1 Feb 2010

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