Haak C S, Hannibal J, Paasch U, Anderson R R, Haedersdal M
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Lasers Surg Med. 2017 Aug;49(6):582-591. doi: 10.1002/lsm.22642. Epub 2017 Feb 9.
Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well-known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown.
Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 μm were generated from micro-needles (0 μm, CZ-0), and AFL (10,600 nm) applied to -80°C deep frozen skin (20 μm, CZ-20) and skin equilibrated to room temperature (80 μm, CZ-80). Channels penetrated into similar mid-dermal skin depths of 600-700 μm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 μm and the transcutaneous permeation was quantified by fluorescence of receptor fluids.
Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ-20 and CZ-80>CZ-0).The thickness of CZ affected PEG distribution in skin. A thin CZ-20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ-80 (PEG 350, 1,000, and 5,000; P < 0.001). In dermis, the uptake through CZ-20 channels was significantly higher than through CZ-80 and CZ-0 at all skin depths (PEG 350, 1,000 and 5,000, 150-1,000 μm; P < 0.001). Correspondingly, transcutaneous permeation of PEG 350 was highest in CZ-20 compared to CZ-80 and CZ-0 samples (P < 0.001). Permeation of larger molecules (PEG 1,000 and PEG 5,000) was generally low.
Uptake of topical compounds is higher through microchannels surrounded by a CZ than without a CZ. Moreover, CZ thickness influences PEG distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582-591, 2017. © 2017 Wiley Periodicals, Inc.
剥脱性分数激光（AFL）在皮肤中产生微通道，其周围是热改变组织区域，称为凝固区（CZ）。CZ的厚度根据应用的波长和激光设置而变化。众所周知，AFL通道有助于局部应用化合物的吸收，但CZ的重要性尚不清楚。
使用Franz扩散池研究平均分子量（MW）为350、1000和5000Da的荧光标记聚乙二醇（PEG）的皮肤吸收和渗透。通过微针（0μm，CZ-0）以及应用于-80°C深度冷冻皮肤（20μm，CZ-20）和平衡至室温的皮肤（80μm，CZ-80）的AFL（10600nm）产生CZ厚度范围为0至80μm的微通道。通道穿透到600 - 700μm的相似真皮中层深度，且每皮肤面积的通道数量相似。在孵育4小时时，通过荧光显微镜在150、400和1000μm的特定皮肤深度评估PEG进入CZ和真皮的皮肤吸收，并通过受体液的荧光对经皮渗透进行定量。
总体而言，与没有CZ的通道相比，被CZ包围的微通道对PEG的吸收最高（CZ-20和CZ-80>CZ-0）。CZ厚度影响PEG在皮肤中的分布。与CZ-80相比，薄的CZ-20在CZ区域内的平均荧光强度明显更高（PEG 350、1000和5000；P<0.001）。在真皮中，在所有皮肤深度处，通过CZ-20通道的吸收均明显高于通过CZ-80和CZ-0的吸收（PEG 350、1000和5000，150 - 1000μm；P<0.001）。相应地，与CZ-80和CZ-0样品相比，PEG 350在CZ-20中的经皮渗透最高（P<0.001）。较大分子（PEG 1000和PEG 5000）的渗透通常较低。
与没有CZ的情况相比，被CZ包围的微通道对局部化合物的吸收更高。此外，CZ厚度影响PEG分布，由薄CZ包围的微通道实现的PEG吸收最高。《激光外科与医学》49:582 - 591，2017年。©2017威利期刊公司
