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.

Background: Topical 5-Fluorouracil (5-FU) exhibits suboptimal efficacy for non-melanoma skin cancer, attributed to insufficient intracutaneous penetration. This study investigates the impact of ablative fractional laser (AFXL) at different laser-channel depths on cutaneous 5-FU pharmacokinetics and biodistribution. Methods: In vitro porcine skin underwent AFXL-exposure using a fractional 10,600 nm CO₂-laser, generating microscopic ablation zones (MAZ) reaching the dermoepidermal junction (MAZ-ED), superficial-(MAZ-DS), or mid-dermis(MAZ-DM). 5-FU in AFXL-exposed and control skin was measured in Franz diffusion cells at 4 and 24 hours (n = 55). HPLC quantified 5-FU in full-thickness skin, specific skin depths of 100μm-1500μm, and transcutaneous receiver-compartments. Qualitative matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) visualized 5-FU in selected samples. Results: Overall, AFXL enhanced and accelerated 5-FU uptake versus unexposed controls, with increased accumulation in deep skin layers (p < 0.01). While total, 24-hour 5-FU uptake in control skin was 0.096 mg/cm³ (0.19% of applied concentration), AFXL delivered up to 4.707 mg/cm³ (MAZ-DM; 9.41% uptake, 49-fold enhancement) (p = 0.002; 24 hours). Indicating accelerated delivery, 5-FU in laser-exposed samples at 4 hours was at least 10-fold that of 24-hour controls (p = 0.002). Deeper laser-channels increased delivery throughout the skin (MAZ-ED vs. MAZ-DM; p<0.01). MALDI-MSI confirmed enhanced, accelerated, deeper and more uniform 5-FU distribution after AFXL versus controls. Conclusions: AFXL offers laser-channel depth-dependent, enhanced and accelerated 5-FU uptake, with increased deposition in deep skin layers.