Chen Bin, Liu Da-Lie, Pan Wen-Yan, Yang Xiao-Hui, Shou Jia-Bao, Wu Ju-Hua, Mao Qing-Long, Wang Jia
Department of Plastic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
Department of Neurosurgery, Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P.R. China.
Mol Med Rep. 2014 Aug;10(2):593-8. doi: 10.3892/mmr.2014.2251. Epub 2014 May 20.
The transdermal delivery system (TDS) is able to obtain a systemic therapeutic effect by administration through the skin, which has low side effects and is able to maintain a sustained blood concentration. However, due to the barrier presented by the stratum corneum, numerous drugs have poor percutaneous permeability. Therefore, the improvement of skin permeability is key to TDS. The main method of promoting transdermal absorption is through the usage of penetration enhancers. Dimethyl sulfoxide (DMSO) is a commonly used penetration enhancer, which has anti‑inflammatory analgesic effects and is able to penetrate the skin. Retinoic acid (RA) and lipolanthionine peptide (LP) may also benefit the permeation efficiency of TDS. Therefore, the present study examined the function of DMSO, RA and LP as penetration enhancers in TDS. Firstly, the optimum concentration of DMSO was confirmed by detecting the expression of the LacZ gene in vitro. Secondly, different combinations of LP, RA and DMSO were applied to mouse skin to analyze the penetration enhancer combination with the greatest efficacy. All the animals were divided into five groups: The RA + LP + DMSO + pORF‑LacZ group, the RA + DMSO + pORF‑LacZ group, the LP + DMSO + pORF‑LacZ group, the DMSO + pORF-LacZ group and the control group. Skin was soaked in combinations of LP, RA and DMSO for seven days and then the pORF‑LacZ plasmids were daubed onto the skin once daily three days. On the 11th day, all the animals were sacrificed by cervical dislocation and the skin and blood samples were collected. The blood samples were used to detect the expression of the LacZ gene by quantitative polymerase chain reaction and the skin samples were used to detect the expression of claudin‑4 and zonula occluden‑1 (ZO‑1) proteins by immunohistochemistry and western blot analysis. The results demonstrated that the combination of LP, RA and DMSO exhibited the greatest transdermal delivery efficiency, which verified that RA and LP were able to increase the penetration effects. Following treatment with LP, the symptoms of dermal edema were relieved and the capillaries contracted, which suggested that LP was a safe and effective penetration enhancer able to reduce the side‑effects caused by DMSO. The present study provides a guideline for the synthesis of novel penetration enhancers.
经皮给药系统（TDS）能够通过皮肤给药获得全身治疗效果，其副作用低且能维持持续的血药浓度。然而，由于角质层形成的屏障，众多药物的经皮渗透性较差。因此，提高皮肤渗透性是TDS的关键。促进透皮吸收的主要方法是使用渗透促进剂。二甲基亚砜（DMSO）是一种常用的渗透促进剂，具有抗炎镇痛作用且能穿透皮肤。维甲酸（RA）和脂环硫肽（LP）也可能有益于TDS的渗透效率。因此，本研究考察了DMSO、RA和LP作为TDS中渗透促进剂的作用。首先，通过体外检测LacZ基因的表达确定DMSO的最佳浓度。其次，将LP、RA和DMSO的不同组合应用于小鼠皮肤，以分析疗效最佳的渗透促进剂组合。所有动物分为五组：RA + LP + DMSO + pORF-LacZ组、RA + DMSO + pORF-LacZ组、LP + DMSO + pORF-LacZ组、DMSO + pORF-LacZ组和对照组。将皮肤浸泡于LP、RA和DMSO的组合中7天，然后连续3天每天在皮肤上涂抹一次pORF-LacZ质粒。在第11天，通过颈椎脱臼处死所有动物并采集皮肤和血液样本。血液样本用于通过定量聚合酶链反应检测LacZ基因的表达，皮肤样本用于通过免疫组织化学和蛋白质印迹分析检测claudin-4和紧密连接蛋白1（ZO-1）的表达。结果表明，LP、RA和DMSO的组合表现出最大的透皮给药效率，这证实RA和LP能够增强渗透效果。用LP处理后，皮肤水肿症状减轻且毛细血管收缩，这表明LP是一种安全有效的渗透促进剂，能够减少DMSO引起的副作用。本研究为新型渗透促进剂的合成提供了指导。
