title: Fractional laser-assisted drug uptake: Impact of time-related topical application to achieve enhanced delivery.
abstract: Ablative fractional laser (AFXL) is acknowledged to increase uptake of topically applied agents in skin. AFXL channels gradually close over time, which may impair this capability. The time frame for applying a drug after AFXL exposure remains to be established. The aim of this study, was to investigate the importance of time-related topical application after AFXL exposure and to relate resultant uptake in skin with AFXL channel morphology and skin integrity.
  
  
  
  Buttock skin of healthy volunteers (n = 11) was exposed to 10,600 nm fractional CO2laser using 5% density, 120 μm beam diameter, 15 mJ pulse energy. Sodium fluorescein (NaF) a small, hydrophilic molecule (370 MW, log P =  -1.52) was applied under standardized conditions at specific time points after laser exposure (0, 2, 5, 10, 30, 60, 90 minute, 6, 24, and 48 hours). Fluorescence photography collected fluorescence images up to 180 minute after NaF application. Optical coherence tomography (OCT) assessed AFXL channel dimensions and transepidermal water loss (TEWL) estimated loss of skin integrity.
  
  
  
  Fluorescence intensities (FI) were significantly elevated when NaF was applied up to 6 hours after laser exposure compared to non-laser-processed skin (median FI 1947 arbitrary units [interquartile range 1,246-3,560] versus 1,004 [350-1,538], P < 0.02). The highest FI occurred when NaF was applied within 30 minute after laser exposure and similar FI were reached for applications at 0, 2, 5, 10, and 30 minute after AFXL exposure (0 minute: 3,866 [3,526-4,575], 30 minute: 3,775 AU [3,070-4,484], P > 0.1). NaF application later than 30 minute after AFXL exposure resulted in gradually decreasing FI, becoming similar to intact skin when applied at 24-48 hours after AFXL exposure (P > 0.2). OCT images demonstrated that AFXL channels closed over time (100% [100-100%] open up to 30 minute, 75% [4-86%] at 6 hours and 3% [0-15%] at 24-48 hours after AFXL exposure). TEWL measurements proved loss of skin integrity up to 6 hours after AFXL exposure, while integrity was similar in laser-exposed and non-laser-exposed skin at 24-48 hours.
  
  
  
  The time frame to maintain enhanced drug delivery sustained for several hours after AFXL exposure, corresponding to channel morphology and loss of skin integrity. Lasers Surg. Med. 49:348-354, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark.|Dermatology Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Banzhaf
authors.affiliation: Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Daniel
authors.initials: D
authors.lastname: Thaysen-Petersen
authors.affiliation: Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Christiane
authors.initials: C
authors.lastname: Bay
authors.affiliation: Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Philipsen
authors.affiliation: Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Mogensen
authors.affiliation: Dermatology Research Centre, The University of Queensland, Brisbane, Australia.
authors.forename: Tarl
authors.initials: T
authors.lastname: Prow
authors.affiliation: Department of Dermatology, University of Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark.
authors.forename: Merete
authors.initials: M
authors.lastname: Haedersdal
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D005260:Female; D019793:Fluorescein / Q000493:pharmacokinetics*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D006801:Humans; D053685:Laser Therapy; D054020:Lasers, Gas; D008297:Male; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects*; D013997:Time Factors; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: D005456:Fluorescent Dyes; D019793:Fluorescein
keywords: fluorescence intensity; imaging; optical coherence tomography; sodium fluorescein; topical drug delivery