Emerging applications of stimulated Raman scattering microscopy for medicinal chemistry and drug discovery

This review article provides a summary of the progress that has been made in the field of stimulated Raman scattering (SRS) microscopy with direct relevance to drug discovery and medicinal chemistry. SRS microscopy is emerging as a powerful technique to visualise drugs and bioactive small molecules in cellular and tissue samples, and recent technological advances coupled with the commercial availability of SRS imaging systems means it has much to offer within preclinical drug evaluation. Attrition rates throughout all stages of the drug discovery pipeline are high and innovative analytical tools have the potential to enhance preclinical evaluation studies. SRS microscopy provides significant capability in pharmaceutical development by providing a label-free and minimally invasive method to determine intracellular drug localisation and metabolism, together with high-resolution images of drug-cell interactions and the ability to visualise any phenotypic cellular response. We summarise the technical developments in hyperspectral SRS microscopy, together with detailing recent applications of machine learning and chemometrics that can be used to extricate underlying biochemical features from imaging data. We outline the developments and applications of SRS imaging for the label-free visualisation of drugs and bioactive small molecules in cellular models, together with an overview of the technique for identifying features of metabolism with relevance to cancer and antimicrobial therapy. Lastly, we cover the application of SRS imaging for transdermal drug delivery and development, before covering pharmaceutical formulation analysis.