Fractional laser-assisted topical delivery leads to enhanced, accelerated and deeper cutaneous 5-fluorouracil uptake
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Fractional laser-assisted topical delivery leads to enhanced, accelerated and deeper cutaneous 5-fluorouracil uptake. / Wenande, Emily; Olesen, Uffe H; Nielsen, Mette M B; Janfelt, Christian; Hansen, Steen Honoré; Anderson, Rox; Haedersdal, Merete.
In: Expert Opinion on Drug Delivery, Vol. 14, No. 3, 2017, p. 307-317.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Fractional laser-assisted topical delivery leads to enhanced, accelerated and deeper cutaneous 5-fluorouracil uptake
AU - Wenande, Emily
AU - Olesen, Uffe H
AU - Nielsen, Mette M B
AU - Janfelt, Christian
AU - Hansen, Steen Honoré
AU - Anderson, Rox
AU - Haedersdal, Merete
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
U2 - 10.1080/17425247.2017.1260119
DO - 10.1080/17425247.2017.1260119
M3 - Journal article
C2 - 27835937
VL - 14
SP - 307
EP - 317
JO - Expert Opinion on Drug Delivery
JF - Expert Opinion on Drug Delivery
SN - 1742-5247
IS - 3
ER -
ID: 168931569