Analysis of time-of-flight secondary ion mass spectrometry data of human skin treated with diclofenac using sparse...

Methods that facilitate molecular identification and imaging are required to evaluate drug penetration into tissues. Time-of-flight secondary ion mass spectrometry (ToF-SIMS), which has high spatial resolution and allows 3D distribution imaging of organic materials, is suitable for this purpose. However, the complexity of ToF-SIMS data, which includes nonlinear factors, makes interpretation challenging. Therefore, in this study, ToF-SIMS data of a stratum corneum treated with diclofenac were analyzed using machine learning to enable the evaluation of drug distribution. Diclofenac-related mass peaks were identified using autoencoder results, and the degree of penetration was evaluated across 2-20^th stripped tapes. In addition, the permeation pathway was clarified by comparing the secondary ion images of phosphatidylethanolamine (PhEA; a marker of the inside of the cell); cholesterol, which is abundant in cell membranes; and diclofenac. Based on the biomolecule-related ion images showing the penetration pathway of diclofenac applied to the skin, diclofenac penetrates both the extracellular space and inside cells.