Karpanen T J, Worthington T, Conway B R, Hilton A C, Elliott T S J, Lambert P A
Life and Health Sciences, Aston University, Aston Triangle B4 7ET, United Kingdom.
Antimicrob Agents Chemother. 2008 Oct;52(10):3633-6. doi: 10.1128/AAC.00637-08. Epub 2008 Aug 1.
This study evaluated a model of skin permeation to determine the depth of delivery of chlorhexidine into full-thickness excised human skin following topical application of 2% (wt/vol) aqueous chlorhexidine digluconate. Skin permeation studies were performed on full-thickness human skin using Franz diffusion cells with exposure to chlorhexidine for 2 min, 30 min, and 24 h. The concentration of chlorhexidine extracted from skin sections was determined to a depth of 1,500 microm following serial sectioning of the skin using a microtome and analysis by high-performance liquid chromatography. Poor penetration of chlorhexidine into skin following 2-min and 30-min exposures to chlorhexidine was observed (0.157 +/- 0.047 and 0.077 +/- 0.015 microg/mg tissue within the top 100 microm), and levels of chlorhexidine were minimal at deeper skin depths (less than 0.002 microg/mg tissue below 300 microm). After 24 h of exposure, there was more chlorhexidine within the upper 100-microm sections (7.88 +/- 1.37 microg/mg tissue); however, the levels remained low (less than 1 microg/mg tissue) at depths below 300 microm. There was no detectable penetration through the full-thickness skin. The model presented in this study can be used to assess the permeation of antiseptic agents through various layers of skin in vitro. Aqueous chlorhexidine demonstrated poor permeation into the deeper layers of the skin, which may restrict the efficacy of skin antisepsis with this agent. This study lays the foundation for further research in adopting alternative strategies for enhanced skin antisepsis in clinical practice.
本研究评估了一种皮肤渗透模型,以确定在局部应用2%(重量/体积)葡萄糖酸氯己定水溶液后,氯己定在全层切除的人体皮肤中的递送深度。使用Franz扩散池对全层人体皮肤进行皮肤渗透研究,使皮肤暴露于氯己定2分钟、30分钟和24小时。在使用切片机对皮肤进行连续切片并通过高效液相色谱分析后,测定从皮肤切片中提取的氯己定浓度,深度可达1500微米。观察到在暴露于氯己定2分钟和30分钟后,氯己定对皮肤的渗透较差(在最上层100微米内为0.157±0.047和0.077±0.015微克/毫克组织),并且在更深的皮肤深度(300微米以下小于0.002微克/毫克组织)氯己定水平极低。暴露24小时后,在最上层100微米切片中有更多的氯己定(7.88±1.37微克/毫克组织);然而,在300微米以下的深度,其水平仍然很低(小于1微克/毫克组织)。未检测到氯己定穿透全层皮肤。本研究中提出的模型可用于体外评估抗菌剂通过皮肤各层的渗透情况。葡萄糖酸氯己定对皮肤深层的渗透较差,这可能会限制该药物用于皮肤消毒的效果。本研究为临床实践中采用替代策略增强皮肤消毒效果的进一步研究奠定了基础。