TY - JOUR

T1 - A Comparison of Human and Porcine Skin in Laser-Assisted Drug Delivery of Chemotherapeutics

AU - Rosenberg, Lukas K.

AU - Bagger, Charlotte

AU - Janfelt, Christian

AU - Haedersdal, Merete

AU - Olesen, Uffe H.

AU - Lerche, Catharina M.

N1 - Special Issue: Dermatology / Plastic Surgery

PY - 2021

Y1 - 2021

N2 - Background and Objectives Porcine skin is a widely used model in diffusion studies, but its usefulness for laser-assisted drug delivery (LADD) has not been evaluated in comparison with human skin. This study compared porcine and human skin in ex vivo LADD diffusion studies.Study Design/Materials and Methods Ex vivo ablative fractional laser (AFL) treatments (5, 20, and 80 mJ/mb) were applied to skin samples from three sources: human, normal pig (Duroc x Landrace x Yorkshire breed), and a hyperkeratotic pig phenotype. Samples were stained using hematoxylin and eosin, photo-documented, and measured digitally. Samples (20 mJ/mb) were exposed to bleomycin or 5-fluorouracil (5-FU) for 19 hours in Franz diffusion cells. Drug uptake was quantified at three skin depths (100, 500, and 1,500 mu m) by high-performance liquid chromatography-mass spectrometry. Drug biodistribution and endogenous lipids were visualized by matrix-assisted laser desorption/ionization-mass spectrometry imaging.Results Epidermal and dermal thicknesses of human and normal pig skin were similar (76-87 mu m and 1,668-1,886 mu m, respectively; P = 0.082-0.494). Endogenous lipids were investigated, and 116 compounds were identified. Of these compounds, 100 were found in all three skin types, while six were present exclusively in human skin. Laser channel depths (20 mJ/mb) in human and normal pig skin were similar (1,081 vs. 1,126 mu m; P = 0.588). Bleomycin uptake was similar in all skin types at all depths (101.4-175.6 mu g/cm(3); P = 0.132-0.699). 5-FU uptake in human and normal pig skin was similar at 100 and 500 mu m (80.5 vs. 140.3 mu g/cm(3) and 131.2 vs. 208.1 mu g/cm(3), respectively; P = 0.065-0.093). At 1500 mu m, 5-FU concentrations in the porcine skin types differed from those in human skin (104.7 vs. 196.7-344.8 mu g/cm(3); P = 0.002-0.026). Drug biodistribution was similar among skin types, but differences between bleomycin and 5-FU biodistribution were observed.Conclusions Normal porcine and human skin showed similar morphology, the composition of endogenous lipids, and AFL-assisted cutaneous uptake, and biodistribution of chemotherapeutics. Therefore, normal porcine skin, but not hyperkeratotic pig phenotype skin, is a practical and reliable model for healthy human skin in ex vivo LADD diffusion studies. Lasers Surg. Med. (c) 2020 Wiley Periodicals LLC

AB - Background and Objectives Porcine skin is a widely used model in diffusion studies, but its usefulness for laser-assisted drug delivery (LADD) has not been evaluated in comparison with human skin. This study compared porcine and human skin in ex vivo LADD diffusion studies.Study Design/Materials and Methods Ex vivo ablative fractional laser (AFL) treatments (5, 20, and 80 mJ/mb) were applied to skin samples from three sources: human, normal pig (Duroc x Landrace x Yorkshire breed), and a hyperkeratotic pig phenotype. Samples were stained using hematoxylin and eosin, photo-documented, and measured digitally. Samples (20 mJ/mb) were exposed to bleomycin or 5-fluorouracil (5-FU) for 19 hours in Franz diffusion cells. Drug uptake was quantified at three skin depths (100, 500, and 1,500 mu m) by high-performance liquid chromatography-mass spectrometry. Drug biodistribution and endogenous lipids were visualized by matrix-assisted laser desorption/ionization-mass spectrometry imaging.Results Epidermal and dermal thicknesses of human and normal pig skin were similar (76-87 mu m and 1,668-1,886 mu m, respectively; P = 0.082-0.494). Endogenous lipids were investigated, and 116 compounds were identified. Of these compounds, 100 were found in all three skin types, while six were present exclusively in human skin. Laser channel depths (20 mJ/mb) in human and normal pig skin were similar (1,081 vs. 1,126 mu m; P = 0.588). Bleomycin uptake was similar in all skin types at all depths (101.4-175.6 mu g/cm(3); P = 0.132-0.699). 5-FU uptake in human and normal pig skin was similar at 100 and 500 mu m (80.5 vs. 140.3 mu g/cm(3) and 131.2 vs. 208.1 mu g/cm(3), respectively; P = 0.065-0.093). At 1500 mu m, 5-FU concentrations in the porcine skin types differed from those in human skin (104.7 vs. 196.7-344.8 mu g/cm(3); P = 0.002-0.026). Drug biodistribution was similar among skin types, but differences between bleomycin and 5-FU biodistribution were observed.Conclusions Normal porcine and human skin showed similar morphology, the composition of endogenous lipids, and AFL-assisted cutaneous uptake, and biodistribution of chemotherapeutics. Therefore, normal porcine skin, but not hyperkeratotic pig phenotype skin, is a practical and reliable model for healthy human skin in ex vivo LADD diffusion studies. Lasers Surg. Med. (c) 2020 Wiley Periodicals LLC

KW - 5&#8208

KW - fluorouracil

KW - bleomycin

KW - endogenous lipids

KW - ex vivo

KW - fractional ablative laser

KW - Franz diffusion cells

KW - laser&#8208

KW - assisted drug delivery

KW - MALDI&#8208

KW - MSI

KW - porcine

KW - TOPICAL DELIVERY

KW - IN-VIVO

U2 - 10.1002/lsm.23344

DO - 10.1002/lsm.23344

M3 - Journal article

C2 - 33161610

VL - 53

SP - 162

EP - 170

JO - Lasers in Surgery and Medicine

JF - Lasers in Surgery and Medicine

SN - 0196-8092

IS - 1

ER -