Franzen Lutz, Anderski Juliane, Windbergs Maike
Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbruecken, Germany.
Saarland University, Department of Biopharmaceutics and Pharmaceutical Technology, Saarbruecken, Germany; Helmholtz Centre for Infection Research (HZI), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Department of Drug Delivery, Saarbruecken, Germany; PharmBioTec GmbH, Saarbruecken, Germany.
Eur J Pharm Biopharm. 2015 Sep;95(Pt A):110-6. doi: 10.1016/j.ejpb.2015.03.026. Epub 2015 Mar 28.
For rational development and evaluation of dermal drug delivery, the knowledge of rate and extent of substance penetration into the human skin is essential. However, current analytical procedures are destructive, labor intense and lack a defined spatial resolution. In this context, confocal Raman microscopy bares the potential to overcome current limitations in drug depth profiling. Confocal Raman microscopy already proved its suitability for the acquisition of qualitative penetration profiles, but a comprehensive investigation regarding its suitability for quantitative measurements inside the human skin is still missing. In this work, we present a systematic validation study to deploy confocal Raman microscopy for quantitative drug depth profiling in human skin. After we validated our Raman microscopic setup, we successfully established an experimental procedure that allows correlating the Raman signal of a model drug with its controlled concentration in human skin. To overcome current drawbacks in drug depth profiling, we evaluated different modes of peak correlation for quantitative Raman measurements and offer a suitable operating procedure for quantitative drug depth profiling in human skin. In conclusion, we successfully demonstrate the potential of confocal Raman microscopy for quantitative drug depth profiling in human skin as valuable alternative to destructive state-of-the-art techniques.
为了合理开发和评估皮肤给药，了解物质渗透入人体皮肤的速率和程度至关重要。然而，目前的分析方法具有破坏性、劳动强度大且缺乏明确的空间分辨率。在此背景下，共聚焦拉曼显微镜有潜力克服当前药物深度剖析的局限性。共聚焦拉曼显微镜已证明其适用于获取定性渗透图谱，但关于其在人体皮肤内进行定量测量的适用性的全面研究仍缺失。在这项工作中，我们开展了一项系统验证研究，以将共聚焦拉曼显微镜用于人体皮肤的定量药物深度剖析。在验证了我们的拉曼显微镜设置后，我们成功建立了一种实验程序，该程序能够将模型药物的拉曼信号与其在人体皮肤中的可控浓度相关联。为了克服当前药物深度剖析中的缺点，我们评估了用于定量拉曼测量的不同峰相关模式，并提供了一种适用于人体皮肤定量药物深度剖析的操作程序。总之，我们成功证明了共聚焦拉曼显微镜在人体皮肤定量药物深度剖析方面的潜力，可作为破坏性的现有技术的有价值替代方法。
