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

https://doi.org/10.1016/j.jaad.2015.12.008Get rights and content

Background

Ablative fractional lasers enhance uptake of topical therapeutics and the concept of fractional laser-assisted drug delivery has now been taken into clinical practice.

Objectives

We systematically reviewed preclinical data and clinical evidence for fractional lasers to enhance drug uptake and improve clinical efficacy.

Methods

We 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.

Results

All 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.

Conclusions

Fractional laser-assisted drug delivery is beneficial in enhancing preclinical and clinical outcomes for certain skin conditions.

Section snippets

Physical enhancement techniques

Physical modulation techniques involve electroporation, iontophoresis, lasers, microdermabrasion, microneedles, pressure, radiofrequency, and sonophoresis (Table I). The armamentarium of techniques has demonstrated improved cutaneous and transcutaneous delivery of various therapeutics, ranging from small drugs (eg, aminolevulinic acid [ALA]6, 7, 8 and methotrexate [MTX]9, 10) to macromolecules exceeding 20,000 Da (eg, human growth hormone11, 12 and erythropoietin13). The literature largely

AFXL-assisted drug delivery

The most commonly used AFXL systems include the erbium-doped yttrium-aluminum-garnet (AFXL; λ = 2940 nm) and the carbon dioxide (AFXL; λ = 10,600 nm) laser. Both lasers operate at infrared wavelengths using water as the target chromophore. AFXL treatments evaporate tissue and leave a matrix of microscopic ablation zones (MAZs) consisting of vertical ablated channels surrounded by a rim of coagulated tissue.16 Specific MAZ profiles depend on the type and power of the laser being used. Channels

Literature search

The PubMed database was searched for the period January 1, 1990, to April 1, 2015, and the Embase database from January 1, 1974, to June 1, 2015. Search terms were: (fractional laser OR ablative fractional laser) AND (drug OR drug delivery OR transdermal delivery OR topical administration). No language or study design restrictions were used. Reference lists of the included manuscripts were examined to obtain additional relevant reports. Studies were included if they reported outcomes regarding

Preclinical studies

Sixteen preclinical trials assessed the relation between laser settings and drug accumulation, using in vitro Franz passive diffusion model (n = 10) and porcine animal models (n = 6) (Table II). Trials evaluated the influence of laser settings on drug deposition in skin, permeation through skin, time-related drug uptake, and drug biodistribution in specific skin layers (Table II). All preclinical trials documented enhanced drug accumulation from fractional laser pretreatment, including

Safety aspects

Drug permeation through AFXL-processed skin may possess harmful effects. Channels provide access to the vascular system, which raises concern about systemic absorption and potential systemic toxicity from topically applied drugs. In particular, serum levels of lidocaine and metabolites were detected in a pig skin model, emphasizing the importance of patient safety.32 AFXL breaks the natural skin barrier, potentially introducing pathogens from the skin surface or from nonsterile topical

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    Funding sources: None.

    Conflicts of interest: None declared.

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