Merete Haedersdal

Fractional CO2 laser‐assisted drug delivery

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.

Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment.

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.

Fractional laser-assisted delivery of methyl aminolevulinate: Impact of laser channel depth and incubation time†

Pretreatment of skin with ablative fractional lasers (AFXL) enhances the uptake of topical photosensitizers used in photodynamic therapy (PDT). Distribution of photosensitizer into skin layers may depend on depth of laser channels and incubation time. This study evaluates whether depth of intradermal laser channels and incubation time may affect AFXL‐assisted delivery of methyl aminolevulinate (MAL).

Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: A critical review from basics to current clinical status

BACKGROUNDnAblative fractional lasers enhance uptake of topical therapeutics and the concept of fractional laser-assisted drug delivery has now been taken into clinical practice.nnnOBJECTIVESnWe systematically reviewed preclinical data and clinical evidence for fractional lasers to enhance drug uptake and improve clinical efficacy.nnnMETHODSnWe searched PubMed and Embase databases; 34 articles met the inclusion criteria. Studies were categorized into experimental preclinical studies and clinical trials, the latter graded according to level of evidence.nnnRESULTSnAll preclinical trials (n = 16) documented enhanced topical drug uptake into skin after ablative fractional laser treatment. Clinical evidence encompassed 18 studies, of which 9 were randomized controlled trials and 2 were controlled trials, examining neoplastic lesions, photodamaged skin, scars, onychomycosis, and topical anesthetics. The highest level of evidence was reached for actinic keratoses treated with methylaminolevulinate for photodynamic therapy (level IB, 5 randomized controlled trials), substantiating superior and long-lasting efficacy versus conventional photodynamic therapy. No adverse events were reported, but ablative fractional laser-assisted drug delivery implies risks of systemic drug absorption, especially when performed over large skin areas.nnnCONCLUSIONSnFractional laser-assisted drug delivery is beneficial in enhancing preclinical and clinical outcomes for certain skin conditions.

Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas – a randomized clinical trial

Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome.

Fractional ablative erbium YAG laser: Histological characterization of relationships between laser settings and micropore dimensions

Treatment of a variety of skin disorders with ablative fractional lasers (AFXL) is driving the development of portable AFXLs. This study measures micropore dimensions produced by a small 2,940u2009nm AFXL using a variety of stacked pulses, and determines a model correlating laser parameters with tissue effects.

Pretreatment with ablative fractional laser changes kinetics and biodistribution of topical 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL)

5‐Aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) are porphyrin precursors used topically for photodynamic therapy (PDT). Previous studies have established that ablative fractional laser (AFXL) increases topical drug uptake. We evaluated kinetics and biodistribution of ALA‐ and MAL‐induced porphyrins on intact and disrupted skin due to AFXL.

Ablative fractional laser alters biodistribution of ingenol mebutate in the skin

Topically applied ingenol mebutate (IngMeb) is approved for field-treatment of actinic keratosis and is currently being investigated for treatment of non-melanoma skin cancer (NMSC). Ablative fractional lasers (AFXLs) generate microscopic ablation zones (MAZs) in the skin, which may help induce a deep penetration needed for effective treatment of NMSC. Using Franz diffusion cells, uptake and bio-distribution were investigated over 21xa0h in intact (nxa0=xa09) and AFXL-exposed porcine skin (nxa0=xa058). A 2940-nm fractional Er:YAG laser generated intraepidermal (11.2xa0mJ/MAZ; 66xa0μm deep, 177xa0μm wide) and intradermal (128xa0mJ/MAZ; 570xa0μm deep, 262 wide) MAZ’s with 16, 97, and 195xa0MAZs/cm2. Surface ablation densities corresponded to 0.5, 2.5, and 5xa0% for intraepidermal MAZs, and corresponded to 1, 5, and 10.5xa0% for intradermal MAZs. Liquid-chromatography–mass-spectrometry quantified deposition of IngMeb in stratum corneum, epidermis, dermis, and receiver chamber. In intact skin, IngMeb readily penetrated to the epidermal layer (1,314xa0ng, 41xa0% of the applied IngMeb), while dermal deposition was limited (508xa0ng, 16xa0%). In AFXL-exposed skin, a profound dermal deposition of IngMeb was achieved, while less accumulated in SC and epidermis. Uptake depended entirely on laser density; increasing coverage from 0xa0% to 0.5xa0%, 1xa0%, 2.5xa0%, 5xa0%, and 10.5xa0% enhanced dermal uptake 1.6-, 2.1-, 3.1-, 3.4-, and 3.9-fold, respectively (pxa0<xa00.0001). Channel depth did not influence drug uptake; at 5xa0% density, dermal deposition with intraepidermal and intradermal MAZs was analogous (1801 vs. 1744; pxa0=xa00.447). In conclusion, IngMeb readily distributes to superficial layers of intact skin, whereas dermal uptake is limited. Independent of channel depth, AFXL enhances dermal drug deposition, providing for customized topical delivery and potential use of IngMeb for treatment of NMSC.

Fractional laser‐assisted drug delivery: Active filling of laser channels with pressure and vacuum alteration

Ablative fractional laser (AFXL) is rapidly evolving as one of the foremost techniques for cutaneous drug delivery. While AFXL has effectively improved topical drug‐induced clearance rates of actinic keratosis, treatment of basal cell carcinomas (BCCs) has been challenging, potentially due to insufficient drug uptake in deeper skin layers. This study sought to investigate a standardized method to actively fill laser‐generated channels by altering pressure, vacuum, and pressure (PVP), enquiring its effect on (i) relative filling of individual laser channels; (ii) cutaneous deposition and delivery kinetics; (iii) biodistribution and diffusion pattern, estimated by mathematical simulation.

Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate

Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser‐channel depth on topical MTX‐delivery.