Haedersdal Merete, Sakamoto Fernanda H, Farinelli William A, Doukas Apostolos G, Tam Josh, Anderson R Rox
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Lasers Surg Med. 2010 Feb;42(2):113-22. doi: 10.1002/lsm.20860.
Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO(2) laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug.
Two Yorkshire swine were treated with single-hole CO(2) laser AFR and subsequent topical application of MAL (Metvix(R), Photocure ASA, Oslo, Norway), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800 microm. AFR was performed with a 10.6 microm wavelength prototype CO(2) laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse.
AFR created cone-shaped channels of approximately 300 microm diameter and 1,850 microm depth that were surrounded by a 70 microm thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P<0.0011) and dermis (P<0.0433) versus MAL alone at skin depths of 120, 500, 1,000, 1,500, and 1,800 microm. AFR before MAL application also enhanced skin surface (epidermal) porphyrin fluorescence. Radial diffusion of MAL from the laser-created channels into surrounding dermis was evidenced by uniform porphyrin fluorescence up to 1,500 microm from the holes (1,000, 1,800 microm depths). Skin massage after MAL application did not affect MAL-induced porphyrin fluorescence after AFR.
Ablative fractional laser treatment facilitates delivery of topical MAL deeply into the skin. For the conditions of this study, laser channels approximately 3 mm apart followed by MAL application could produce porphyrins throughout essentially the entire skin. AFR appears to be a clinically practical means for enhancing uptake of MAL, a photodynamic therapy drug, and presumably many other topical skin medications.
剥脱性点阵激光换肤术（AFR）可形成垂直通道，这可能有助于将局部应用的药物输送到皮肤中。本研究的目的是使用卟啉前体5-氨基酮戊酸甲酯（MAL）作为测试药物，评估二氧化碳激光AFR的药物递送情况。
对两只约克夏猪进行单孔二氧化碳激光AFR治疗，随后局部应用MAL（Metvix®，Photocure ASA，挪威奥斯陆）、安慰剂乳膏且不使用药物。通过荧光显微镜在低至1800微米的皮肤深度测量MAL诱导的卟啉荧光。使用波长为10.6微米的原型二氧化碳激光进行AFR，采用3毫秒的堆叠单脉冲，每个脉冲能量为91.6毫焦。
AFR形成了直径约300微米、深度1850微米的锥形通道，通道周围有一层70微米厚的热凝真皮薄层。安慰剂乳膏或未治疗的皮肤部位没有卟啉荧光。AFR后应用MAL可增强药物递送，与单独应用MAL相比，在120、500、1000、1500和1800微米的皮肤深度处，毛囊（P<0.0011）和真皮（P<0.0433）的卟啉荧光显著更高。在应用MAL之前进行AFR也可增强皮肤表面（表皮）的卟啉荧光。从激光形成的通道向周围真皮的MAL径向扩散表现为距孔1500微米（1000、1800微米深度）范围内均匀的卟啉荧光。应用MAL后进行皮肤按摩对AFR后MAL诱导的卟啉荧光没有影响。
剥脱性点阵激光治疗有助于将局部应用的MAL深入递送至皮肤。在本研究条件下，间隔约3毫米的激光通道后应用MAL可在基本上整个皮肤中产生卟啉。AFR似乎是一种临床上切实可行的方法，可增强光动力治疗药物MAL以及大概许多其他局部皮肤药物的摄取。
