Fractional CO2 laser-assisted drug delivery

Authors

  • Merete Hædersdal MD, PhD, DMSc,

    Corresponding author
    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
    2. Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen 2400, Denmark
    • Wellman Center for Photomedicine, Harvard Medical School, Massachusetts General Hospital, BHX 630-55 Fruit Street Boston, MA 02114.
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  • Fernanda H. Sakamoto MD,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
    2. Department of Dermatology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP 04023-900, Brazil
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  • William A. Farinelli BA,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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  • Apostolos G. Doukas PhD,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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  • Josh Tam PhD,

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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  • R. Rox Anderson MD

    1. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114
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  • Merete Hædersdal and Fernanda H. Sakamoto contributed equally to this work.

  • None of the authors listed have any conflict of interest, regarding this publication.

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 µm wavelength 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 µm 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. Lasers Surg. Med. 42:113–122, 2010. © 2009 Wiley-Liss, Inc.

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