Department of Dermatology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Nielsine Nielsens Vej 17, entrance 9, 2. floor, Copenhagen, Nordvest, DK-2400, Denmark.
Department of Dermatology, Erasmus MC University Medical Center Rotterdam, Dr. Molewaterplein 40, Rotterdam, 3015, The Netherlands.
Lasers Surg Med. 2021 Jul;53(5):622-629. doi: 10.1002/lsm.23326. Epub 2020 Oct 1.
Thermo-mechanical fractional injury (TMFI) impacts the skin barrier and may increase cutaneous drug uptake. This study investigated the potential of TMFI in combination with 5-aminolevulinic acid (ALA) cream and gel formulations to enhance Protoporphyrin IX (PpIX) fluorescence at the skin surface and in the skin.
STUDY DESIGN/MATERIALS AND METHODS: In healthy volunteers (n = 12) a total of 144 test areas were demarcated on the upper back. Test areas were randomized to (i) TMFI (6 milliseconds, 400 µm at a single pass) or no pretreatment and (ii) 20% ALA in cream or gel formulations. Skin surface PpIX fluorescence was quantified by PpIX fluorescence photography and photometry in 30-minute intervals until 3 hours. PpIX fluorescence microscopy quantified separate PpIX fluorescence in the epidermis, and in superficial-, mid-, and deep- dermis from punch biopsies sampled after 3 hours of ALA incubation. Local skin reactions (LSR) and pain intensities (numerical rating scale 0-10) were evaluated immediately, at 3 hours and 14 days after the intervention.
TMFI exposure before photosensitizer application significantly increased skin surface PpIX fluorescence, both for ALA cream (TMFI-ALA-cream 7848 arbitrary units [AU] vs. ALA-cream 5441 AU, 3 hours, P < 0.001) and ALA gel (TMFI + ALA-gel 4591 AU vs. ALA-gel 3723 AU, 3 hours, P < 0.001). The TMFI-mediated increase in PpIX fluorescence was similar for ALA-cream and -gel formulations (P = 0.470) at the skin surface. In the epidermis, PpIX fluorescence intensities increased from combination treatment with TMFI and ALA-cream (TMFI + ALA-cream 421 AU vs. ALA-cream 293 AU, P = 0.034) but not from combination with TMFI and ALA-gel (TMI + ALA-gel 264 AU vs. ALA-gel 261 AU, P = 0.791). Dermal fluorescence intensities (superficial-, mid-, or deep dermis) were unaffected by TMFI pretreatment in both ALA-cream and ALA-gel exposed skin (P = 0.339). ALA-cream generally induced higher PpIX fluorescence intensities than ALA-gel (skin surface P < 0.001 and epidermis P < 0.03). TMFI induced low pain intensities (median 3) and mild LSR that were resolved at 14 days follow-up.
Given the present study design, TMFI, in combination with the standardized application of 20% ALA cream and gel formulations, significantly enhanced skin surface PpIX fluorescence compared to no pretreatment. Additionally, TMFI increased epidermal PpIX fluorescence combined with 20% ALA cream vehicle. Thus, TMFI pretreatment and formulation characteristics exert influence on PpIX fluorescence intensities in normal skin. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.
热机械分数损伤（TMFI）会影响皮肤屏障，可能会增加皮肤的药物摄取。本研究探讨了 TMFI 联合 5-氨基酮戊酸（ALA）乳膏和凝胶制剂在增加皮肤表面和皮肤中原卟啉 IX（PpIX）荧光方面的潜力。
研究设计/材料和方法：在健康志愿者（n=12）的上背部共标记了 144 个测试区域。测试区域随机分为（i）TMFI（6 毫秒，单次通过时 400μm）或无预处理，和（ii）20% ALA 的乳膏或凝胶制剂。通过 PpIX 荧光摄影术和光度法在 30 分钟的间隔内量化皮肤表面的 PpIX 荧光，直到 3 小时。使用 PpIX 荧光显微镜从 3 小时 ALA 孵育后采集的打孔活检中量化表皮和表皮浅层、中层和深层中的单独 PpIX 荧光。立即、3 小时和干预后 14 天评估局部皮肤反应（LSR）和疼痛强度（数字评分 0-10）。
与单独使用 ALA 乳膏（TMFI-ALA-cream 7848 个任意单位 [AU] 与 ALA-cream 5441 AU，3 小时，P < 0.001）和 ALA 凝胶（TMFI+ALA-gel 4591 AU 与 ALA-gel 3723 AU，3 小时，P < 0.001）相比，光敏剂应用前的 TMFI 暴露显著增加了皮肤表面的 PpIX 荧光。TMFI 介导的 PpIX 荧光增加在 ALA 乳膏和凝胶制剂中相似（P=0.470）。在表皮中，与单独使用 ALA 乳膏（TMFI+ALA-cream 421 AU 与 ALA-cream 293 AU，P=0.034）相比，TMFI 与 ALA-cream 的联合治疗增加了 PpIX 荧光强度，但与 TMFI 与 ALA-凝胶的联合治疗没有（TMI+ALA-gel 264 AU 与 ALA-gel 261 AU，P=0.791）。两种 ALA 乳膏和凝胶暴露皮肤的真皮荧光强度（表皮浅层、中层或深层）不受 TMFI 预处理的影响（P=0.339）。与 ALA 凝胶相比，ALA 乳膏通常诱导更高的 PpIX 荧光强度（皮肤表面 P < 0.001 和表皮 P < 0.03）。TMFI 诱导的疼痛强度较低（中位数为 3），轻度 LSR 在 14 天随访时得到解决。
根据本研究设计，与无预处理相比，TMFI 联合使用标准化的 20% ALA 乳膏和凝胶制剂可显著增强皮肤表面的 PpIX 荧光。此外，TMFI 联合 20% ALA 乳膏载体增加了表皮 PpIX 荧光。因此，TMFI 预处理和制剂特性会影响正常皮肤中的 PpIX 荧光强度。激光外科学杂志。© 2020 威利父子公司。
