Xin Yue, Wen Xiang, Hamblin Michael R, Jiang Xian
Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, China.
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.
J Cosmet Dermatol. 2021 Feb;20(2):626-635. doi: 10.1111/jocd.13581. Epub 2020 Aug 17.
Topical anesthetics are widely used in dermatology and cosmetology to alleviate the pain from nonsurgical cosmetic procedures, while the transdermal drug delivery is limited by the skin barrier. Cold atmospheric plasma (CAP) is a potential approach used for skin pretreatment to enhance transdermal delivery of topical medications.
To assess the efficacy of CAP as a pretreatment to improve the transdermal delivery of topical anesthetic.
First, we conducted ex vivo permeation studies on 30 mice with a Franz cell diffusion experiment. CAP irradiations of different intensity and duration were pretreated on the epidermal layer of mice before topical lidocaine applied, with the control group received no pretreatment. The amount of drug penetrated through the skin and drug flux were determined by high-performance liquid chromatography. Then, we treated 3 living mice with CAP followed by application of methylene blue cream (MB) and used skin biopsies to measure penetration depth by microscope. Last, we measured the transepidermal water loss (TEWL) of mouse skin in vivo before and after CAP treatment to observe its effect on the skin barrier function.
In the permeation study, the transdermal flux of lidocaine was enhanced to 1.97 times of the control samples by CAP pretreatment. We also observed that the accumulative amount of lidocaine varied with the duration of the CAP treatment in a biphasic manner. In the MB penetration study, significant amount of MB deposition was observed under the epidermis and deeper parts of the skin after CAP pretreatment compared with the control sample. A sharp increase in TEWL value was observed directly after the CAP treatment, but 30 minutes later, it began to decrease and recovered to baseline in the next 3 hours, indicating that the skin barrier property had been changed reversibly.
Our studies suggested that the transdermal absorption of topical lidocaine can be efficiently and safely enhanced by pretreatment of the skin with CAP. We believe that CAP could be used as an assistance to improve analgesia in dermatology.
局部麻醉剂在皮肤科和美容领域被广泛用于减轻非手术美容程序带来的疼痛，然而经皮给药受到皮肤屏障的限制。冷大气等离子体（CAP）是一种用于皮肤预处理以增强局部药物经皮递送的潜在方法。
评估CAP作为预处理手段改善局部麻醉剂经皮递送的效果。
首先，我们使用Franz细胞扩散实验对30只小鼠进行了离体渗透研究。在局部应用利多卡因之前，对小鼠的表皮层进行不同强度和持续时间的CAP照射，对照组不进行预处理。通过高效液相色谱法测定透过皮肤的药物量和药物通量。然后，我们对3只活体小鼠进行CAP处理，随后涂抹亚甲蓝乳膏（MB），并通过显微镜检查皮肤活检样本以测量渗透深度。最后，我们在CAP处理前后测量小鼠皮肤的经表皮水分流失（TEWL），以观察其对皮肤屏障功能的影响。
在渗透研究中，CAP预处理使利多卡因的经皮通量提高到对照样品的1.97倍。我们还观察到利多卡因的累积量随CAP处理持续时间呈双相变化。在MB渗透研究中，与对照样品相比，CAP预处理后在表皮下方和皮肤更深部位观察到大量MB沉积。CAP处理后立即观察到TEWL值急剧增加，但30分钟后，它开始下降并在接下来的3小时内恢复到基线，表明皮肤屏障特性发生了可逆变化。
我们的研究表明，通过CAP对皮肤进行预处理可以有效且安全地增强局部利多卡因的经皮吸收。我们认为CAP可作为改善皮肤科镇痛效果的辅助手段。
