Haak Christina S, Farinelli William A, Tam Joshua, Doukas Apostolos G, Anderson R Rox, Haedersdal Merete
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark.
Lasers Surg Med. 2012 Dec;44(10):787-95. doi: 10.1002/lsm.22102. Epub 2012 Dec 4.
Pretreatment of skin with ablative fractional lasers (AFXL) enhances the uptake of topical photosensitizers used in photodynamic therapy (PDT). Distribution of photosensitizer into skin layers may depend on depth of laser channels and incubation time. This study evaluates whether depth of intradermal laser channels and incubation time may affect AFXL-assisted delivery of methyl aminolevulinate (MAL).
Yorkshire swine were treated with CO2 AFXL at energy levels of 37, 190, and 380 mJ/laser channel and subsequent application of MAL cream (Metvix) for 30, 60, 120, and 180 minutes incubation time. Fluorescence photography and fluorescence microscopy quantified MAL-induced porphyrin fluorescence (PpIX) at the skin surface and at five specific skin depths (120, 500, 1,000, 1,500, and 1,800 µm).
Laser channels penetrated into superficial (∼300 µm), mid (∼1,400 µm), and deep dermis/upper subcutaneous fat layer (∼2,100 µm). Similar fluorescence intensities were induced at the skin surface and throughout skin layers independent of laser channel depth (180 minutes; P < 0.19). AFXL accelerated PpIX fluorescence from skin surface to deep dermis. After laser exposure and 60 minutes MAL incubation, surface fluorescence was significantly higher compared to intact, not laser-exposed skin at 180 minutes (AFXL-MAL 60 minutes vs. MAL 180 minutes, 69.16 a.u. vs. 23.49 a.u.; P < 0.01). Through all skin layers (120-1,800 µm), laser exposure and 120 minutes MAL incubation induced significantly higher fluorescence intensities in HF and dermis than non-laser exposed sites at 180 minutes (1,800 µm, AFXL-MAL 120 minutes vs. MAL 180 minutes, HF 14.76 a.u. vs. 6.69 a.u. and dermis 6.98 a.u. vs. 5.87 a.u.; P < 0.01).
AFXL pretreatment accelerates PpIX accumulation, but intradermal depth of laser channels does not affect porphyrin accumulation. Further studies are required to examine these findings in clinical trials.
用剥脱性点阵激光（AFXL）预处理皮肤可增强光动力疗法（PDT）中局部光敏剂的摄取。光敏剂在皮肤各层中的分布可能取决于激光通道的深度和孵育时间。本研究评估皮内激光通道深度和孵育时间是否会影响AFXL辅助的氨基乙酰丙酸甲酯（MAL）递送。
对约克夏猪使用能量水平为37、190和380 mJ/激光通道的二氧化碳AFXL进行治疗，随后涂抹MAL乳膏（Metvix），孵育时间分别为30、60、120和180分钟。通过荧光摄影和荧光显微镜对皮肤表面及五个特定皮肤深度（120、500、1000、1500和1800 µm）处MAL诱导的卟啉荧光（PpIX）进行定量。
激光通道可穿透至浅表真皮（约300 µm）、中层真皮（约1400 µm）以及深层真皮/皮下脂肪上层（约2100 µm）。在皮肤表面和各皮肤层诱导的荧光强度相似，与激光通道深度无关（孵育180分钟；P < 0.19）。AFXL可加速PpIX荧光从皮肤表面向深层真皮的转移。激光照射后MAL孵育60分钟时，表面荧光显著高于未进行激光照射的完整皮肤在180分钟时的荧光（AFXL - MAL 60分钟 vs. MAL 180分钟，69.16任意单位 vs. 23.49任意单位；P < 0.01）。在所有皮肤层（120 - 1800 µm）中，激光照射后MAL孵育120分钟时，毛囊和真皮中的荧光强度显著高于未进行激光照射的部位在180分钟时的荧光（1800 µm处，AFXL - MAL 120分钟 vs. MAL 180分钟，毛囊14.76任意单位 vs. 6.69任意单位，真皮6.98任意单位 vs. 5.87任意单位；P < 0.01）。
AFXL预处理可加速PpIX的积累，但皮内激光通道深度不影响卟啉的积累。需要进一步开展研究在临床试验中验证这些发现。
