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 10,600nm 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 0.096mg/cm(3)(0.19% of applied concentration),AFXL delivered up to 4.707mg/cm(3)(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.