14:10 - 15:30
Wed-Hall 2-8A
Hall 2
Podium Session
Imaging skin-penetration dynamics of caffeine under various conditions by using a high-resolution non-invasive analytical method
Podium 53
Presented by: Risa Iguchi
Risa Iguchi 1, Terumasa Ito 2, Yoji Nishi 1, Tsuyoshi Ogihara 1, Kazuhiko Misawa 2
1 Matsumoto Trading Co.,Ltd., Tokyo
2 Tokyo University of Agriculture and Technology, Tokyo
Evaluating the penetration and distribution profiles of applied actives within the skin is essential for developing actives and cosmetic formulations. Recent advances in label-free imaging technologies have facilitated the direct detection of unlabeled chemicals in tissues. However, real-time quantitative monitoring and obtaining dynamic information during the penetration processes within the complex tissues is still a challenge. We have previously reported the label-free evaluation of skin penetration profiles of several actives in an epidermis skin model using a newly developed setup of pump-probe phase-modulated stimulated Raman scattering (PM-SRS) microscopy combined with confocal reflection microscopy [1,2]. PM-SRS microscopy is a unique imaging tool that minimizes strong background signals through a pulse-shaping technique and provides high-contrast imaging of small molecules in tissues.
In this study, using this advanced imaging system, we aimed to visualize and compare the penetration dynamics of caffeine under several conditions. We compared the penetration profiles of caffeine in vitro and ex vivo, since it is well known that the barrier functions of human epidermis models and the human skin are not the same. We further investigated the influence of different sizes of liposomes on the delivery, penetration and retention of caffeine in excised human skin.
Excised human skin samples and reconstructed human epidermis models were used for skin penetration analysis. Caffeine was chosen as a model drug due to its aqueous solubility and a relatively low molecular weight. Skin penetration profiles of caffeine in vitro and ex vivo from an aqueous solution and liposome formulations were analyzed using a combination of PM-SRS and confocal reflection microscopy. Liposomes for this study were formulated by the conventional high-pressure homogenization method.
We directly detected the characteristic Raman signal of caffeine in the human epidermis model and excised human skin by PM-SRS. Combining PM-SRS and confocal reflection microscopy provided the real-time concentration profiles of caffeine from formulations within the tissues by lowering the background signals from skin tissue and increasing the signal-to-noise ratio. We succeeded in imaging the difference in the penetration profiles of caffeine in vitro and ex vivo. We further understood the influence of the size of liposomes on the delivery and retention of caffeine in human skin.
PM-SRS microscopy is a powerful, non-invasive, real-time depth-profile imaging method for the quantitative studies of topically applied actives.

1) Iguchi R, Nishi Y, Ogihara T, Ito T, Matsuoka F, Misawa K. Skin Res Technol. 2021. Epub ahead of print.
2) Ito T, Iguchi R, Matsuoka F, Nishi Y, Ogihara T, Misawa K. Biomed Opt Express. 2021;12(10):6545-6557.