Li Zhuo-Heng, Li Yuan-Yuan, Hou Min, Yang Tao, Lu Lai-Chun, Xu Xiao-Yu
College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, 400715, People's Republic of China.
Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing, 400715, People's Republic of China.
Lasers Med Sci. 2018 Aug;33(6):1279-1286. doi: 10.1007/s10103-018-2479-8. Epub 2018 Jun 13.
Hypericin, a powerful natural photosensitizer in photodynamic therapy (PDT), is suitable for treating skin diseases involving excess capillary proliferation. In the present study, we aimed to evaluate the skin penetrability of topically applied hypericin, expecting a reduced risk of prolonged skin photosensitivity, which often occurs after systemic administration. Firstly, the Franz diffusion cell assays were performed to evaluate the penetration effects of different enhancers, including menthol, propylene glycol, camphanone, azone, and carbamide. In view of above evaluation results, we selected menthol as the enhancer in the subsequent in vivo studies. The setting groups were as follows: the blank control group, the light-exposure control group, the gel-base control group, the hypericin gel group, and a hypericin gel-containing menthol group. Except for the blank control, all other animals were irradiated by a LED light. Then, fluorescence microscopy was performed to examine the distribution of hypericin in the skin of nude mouse. Macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment. Immunohistochemistry was used to determine the expression change of PECAM-1. As shown in the results, menthol facilitated hypericin penetrate the skin of nude mice most. The results of in vivo assays revealed that hypericin penetrated nude mouse skin, spread to the dermis, and resulted in obvious photosensitivity reaction on the dermal capillaries. Moreover, skin injured by the photosensitive reaction induced by hypericin-PDT treatment was replaced by normal skin within 7 days. We concluded that topical applied hypericin could penetrate nude mouse skin well and has a great potential in PDT treatment of skin diseases.
金丝桃素是光动力疗法（PDT）中一种强大的天然光敏剂，适用于治疗涉及毛细血管过度增生的皮肤病。在本研究中，我们旨在评估局部应用金丝桃素的皮肤渗透性，期望降低全身给药后经常出现的皮肤光敏性延长的风险。首先，进行了Franz扩散池试验，以评估不同增强剂（包括薄荷醇、丙二醇、樟脑、氮酮和尿素）的渗透效果。鉴于上述评估结果，我们在随后的体内研究中选择薄荷醇作为增强剂。设置的组如下：空白对照组、光照对照组、凝胶基质对照组、金丝桃素凝胶组和含薄荷醇的金丝桃素凝胶组。除空白对照组外，所有其他动物均用LED灯照射。然后，进行荧光显微镜检查以检测金丝桃素在裸鼠皮肤中的分布。还进行了宏观和微观分析，以检测局部应用金丝桃素 - PDT治疗后皮肤的病理变化。免疫组织化学用于确定PECAM - 1的表达变化。结果表明，薄荷醇最有助于金丝桃素穿透裸鼠皮肤。体内试验结果显示，金丝桃素穿透裸鼠皮肤，扩散至真皮，并在真皮毛细血管上引起明显的光敏反应。此外，金丝桃素 - PDT治疗引起的光敏反应损伤的皮肤在7天内被正常皮肤替代。我们得出结论，局部应用金丝桃素可很好地穿透裸鼠皮肤，在皮肤病的PDT治疗中具有很大潜力。
