Abstract
The penetration behavior of topical substances in the skin not only relates to the transdermal delivery efficiency but also involves the safety and therapeutic effect of topical products, such as sunscreen and hair growth products. Researchers have tried to illustrate the transdermal process with diversified theories and technologies. Directly observing the distribution of topical substances on skin by characteristic imaging is the most convincing approach. Unfortunately, fluorescence labeling imaging, which is commonly used in biochemical research, is limited for transdermal research for most topical substances with a molecular mass less than 500 Da. Label-free imaging technologies possess the advantages of not requiring any macromolecular dyes, no tissue destruction and an extensive substance detection capability, which has enabled rapid development of such technologies in recent years and their introduction to biological tissue analysis, such as skin samples. Through the specific identification of topical substances and endogenous tissue components, label-free imaging technologies can provide abundant tissue distribution information, enrich theoretical and practical guidance for transdermal drug delivery systems. In this review, we expound the mechanisms and applications of the most popular label-free imaging technologies in transdermal research at present, compare their advantages and disadvantages, and forecast development prospects.