Soft X-ray scanning transmission microscopy as a selective probe of topical dermal drug delivery: The role of petrolatum and occlusion

Selective and label-free probing of drugs by scanning transmission X-ray microscopy (STXM) is applied along with hyperspectral imaging to probe topically applied drugs in human skin explants ex vivo. A comparison of data evaluation strategies is reported, which includes changes in optical density at selected photon energies in the O 1 s regime, linear combination modeling using reference spectra, as well as principal component and cluster analyses. It is shown that consistent results are obtained from linear combination modeling of reference spectra and changes in optical density. The dermal penetration of the anti-inflammatory drug rapamycin is investigated with high spatial resolution using a petrolatum-based formulation. For such well-known formulation the result of occlusion is investigated leading to drug uptake into corneocytes. Additional changes in drug penetration induced by weakening the skin barrier by the serine protease trypsin are also included. These results are discussed in comparison with the dermal penetration of other drug formulations. Finally, alternatives to present data acquisition strategies in STXM are discussed with respect to sub-sampling in combination with mathematical approaches, so that the full chemical and spatial information can be retrieved and radiation damage is minimized.