{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T16:39:28Z","timestamp":1787330368437,"version":"build-2736575974"},"reference-count":46,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Skin Pharmacol Physiol"],"abstract":"<jats:p>Background: A holy grail in human skin permeation is to be able to quantify how compounds and nanoparticles are absorbed, distributed, and exert their effects. Traditionally, the processes used have either been destructive or relied upon interpreting what has exited the skin after absorption, be it in in vivo plasma or urine or through ex vivo skin. Multiphoton imaging and other modalities have revolutionized this landscape. Summary: In this review article, we summarize our experiences in using multiphoton tomography and fluorescence lifetime imaging in characterizing the skin absorption, distribution, and redox effects of nanoparticulate and related delivery systems. Much of our work has been focused on the absorption and safety of nano zinc oxide which started off being an apparently unsafe product to now being an FDA GRAS substance. We have found that the skin is a remarkable physical barrier to zinc oxide nanoparticles, as well as to other nanoparticles, under a wide range of formulation and method of use conditions. However, this work has only been made possible for us by the development of confocal, multiphoton, and fluorescence lifetime imaging technologies that can be safely used on human skin. Key messages: (1) Multiphoton tomography and fluorescence lifetime imaging have allowed us, for the first time, to safely image the transport of compounds and structures in human skin in vivo and to assess the redox state of the skin after that application. (2) A key use of this instrumentation and related techniques has been to show that the sunscreen, nano zinc oxide, is generally safe when applied to human skin in various formulations and under a wide range of conditions. (3) We have also shown that characterizing nano-zinc oxide skin absorption by urinary zinc isotope excretion is misleading because, in our experience, zinc oxide nanoparticles are hydrolyzed to zinc ions which are readily absorbed into the viable epidermis and will be excreted in the urine. (4) We have also shown other nanoparticles, such as quantum dots, silver, and gold, are poorly absorbed into the skin. (5) However, our imaging does show that nanoparticles can accumulate and be difficult to wash out of skin furrows and hair follicles, creating a reservoir effect. (6) While this review has emphasized studies exploring the safety of topical ZnO-NP and related materials, we have also shown that multiphoton tomography and related techniques may be used in the quality, therapeutic, and theranostic assessment of topical products.<\/jats:p>","DOI":"10.1159\/000553032","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T16:01:22Z","timestamp":1782403282000},"page":"1-15","source":"Crossref","is-referenced-by-count":0,"title":["Multiphoton Tomography of Micro- and Nanocosmetics in Human Skin: In vivo Studies in Volunteers and Patients with ex vivo Validation"],"prefix":"10.1159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4686-9006","authenticated-orcid":false,"given":"Ana Carolina","family":"Henriques Ribeiro 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