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

Abstract

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 × Landrace × 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 µm) 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 µm and 1,668–1,886 µm, 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 µm; P = 0.588). Bleomycin uptake was similar in all skin types at all depths (101.4–175.6 µg/cm3; P = 0.132–0.699). 5‐FU uptake in human and normal pig skin was similar at 100 and 500 µm (80.5 vs. 140.3 µg/cm3 and 131.2 vs. 208.1 µg/cm3, respectively; P = 0.065–0.093). At 1500 µm, 5‐FU concentrations in the porcine skin types differed from those in human skin (104.7 vs. 196.7–344.8 µg/cm3; 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. © 2020 Wiley Periodicals LLC

Optical Imaging Visualizes a Homogeneous and Horizontal Band-Like Biodistribution of Large- and Small-Size Hydrophilic Compounds Delivered by Ablative Fractional Laser

“…In their study, they observed a deeper laser channel depth of 70 µm using OCT. The epidermal thickness was not measured in the ICG-delivery study, but a recent study found a median depth of 76 µm in abdominal human skin [ 25 ]; thus, the channels might not penetrate through the epidermis similar to our study on pig skin. The different channel depths could be due to differences in the hydration of the skin, the resolution of the OCT or deviations in the laser beam angle to the focal plane of the skin, which has been shown to have a great impact on the laser channel morphometrics [ 26 ].…”

“…One recent study investigated the delivery of the fluorescent molecule indocyanine green (ICG) with a fractional CO 2 laser also using 2.5 mJ/mb and 5% density. Even though they used ex vivo human skin [ 24 ], it was shown that drug biodistribution among human and pig skin is similar [ 25 ]. In their study, they observed a deeper laser channel depth of 70 µm using OCT.…”

A one‐time pneumatic jet‐injection of 5‐fluorouracil and triamcinolone acetonide for treatment of hypertrophic scars—A blinded randomized controlled trial

“…Biopsies were embedded in water, cryosectioned in 10 µm vertical samples, and stored at −80°C until MALDI‐MSI analysis. The distribution of 5‐FU was qualitatively determined by the same MALDI‐MSI method as described previously by the authors 23 . The samples were imaged on a QExactive Orbitrap mass spectrometer (Thermo Fischer Scientific) equipped with a SMALDI5 ion source (TransMIT GmbH).…”

“…The distribution of 5-FU was qualitatively determined by the same MALDI-MSI method as described previously by the authors. 23 The samples were imaged on a QExactive Orbitrap mass spectrometer (Thermo Fischer Scientific) equipped with a SMALDI5 ion source (TransMIT GmbH). Imaging was performed in line mode at a pixel size of 20 µm using a scan range of m/z 127-900 in negative-ion mode.…”

Bleomycin administered by laser-assisted drug delivery or intradermal needle-injection results in distinct biodistribution patterns in skin: in vivo investigations with mass spectrometry imaging

“…When used to treat BCCs, intralesional BLM is currently administered by conventional needle injection (NI) to overcome the skin barrier. Several alternative drug delivery systems that may be used to treat BCCs have been tested, including hollow micro-needles (Sabri et al, 2020 ), pneumatic injection (Erlendsson et al, 2020 ; Bik et al, 2021 ; Rosenberg et al, 2021 ), and laser-assisted drug delivery (LADD) (Wenande et al, 2021 ). Ablative fractional laser (AFL) has been shown to facilitate and enhance topical BLM delivery via LADD ex vivo and is a prime candidate for BLM drug delivery due to its intrinsically therapeutic effect on BCCs (Mirza and Khatri, 2017 ; Hendel et al, 2019 ; Navarrete-Dechent, 2019 ).…”