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