Label-Free Analysis of Drug Delivery Systems and Cellular Interaction Studies Using Confocal Raman Microscopy

In pharmaceutical development many questions still remain unsolved despite the availability of many analytical techniques. Consequently, the need of novel analytical approaches is not yet satisfied. In this thesis, confocal Raman microscopy is utilized to fill the scientific gap. In fact, the benefit of this non-destructive, label-free visualization technique for profound analysis in complex pharmaceutical applications is successfully demonstrated. The impact of drying on drug distribution is proven by localizing the drug in wet-extruded pellets with Raman imaging. Additionally to this finding, the correlation between drug distribution and release is successfully elucidated. For the first time, confocal Raman microscopy is combined with optical profilometry. Thus, the limitations of the confocal microscope are overcome and all-encompassing component visualization in complex drug delivery systems exhibiting challenging structured surfaces is realized. During development of a lipid-based drug permeation model, the successive formation of the permeation barrier during coating is finally described using Raman analysis. Investigations benefit tremendously from a combination of chemical imaging in lateral and vertical planes to depict barrier integrity and stability. Finally, human cells as well as the uptake of different nanoparticles are analyzed label-free in aqueous environment, utilizing linear and coherent Raman techniques.