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Nitric oxide (NO), a gaseous mediator with a very relevant role in many physiological and pathophysiological processes, is expected to complement the functions of HA in the skin through its vasodilatory, anti\u2010inflammatory, and regenerative properties. Herein, a novel class of HA derivatives functionalized with NO photodonors (NOPD) for light\u2010activated therapeutic applications is introduced. The HA derivatives HA\u2010NOPD1 and HA\u2010NOPD2 demonstrated NO release under blue light activation. Biological assays on HaCaT keratinocytes revealed enhanced proliferation and migration under light stimuli, underscoring the therapeutic potential of HA\u2010NOPD1. The derivatives are formulated into microemulsions (MEs) to allow their skin transport. MEs loaded with the photoresponsive derivatives are stable in the dark and provide effective NO photorelease with higher quantum yields than the free compounds. Skin permeation studies using porcine and artificial membranes confirmed that HA\u2010NOPD2 distributed in all the skin layers, reaching the dermis and releasing NO in situ.<\/jats:p>","DOI":"10.1002\/adhm.202500589","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T08:17:00Z","timestamp":1748333820000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Light\u2010Activatable Hyaluronic Acid\u2010Derivatives Releasing Nitric Oxide and Their Delivery in the Skin"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4617-5546","authenticated-orcid":false,"given":"Giuseppe","family":"Longobardi","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Napoli Federico II  Via Domenico Montesano 49 Napoli I\u201080131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7285-9442","authenticated-orcid":false,"given":"Cristina","family":"Parisi","sequence":"additional","affiliation":[{"name":"PhotoChemLab Department of Drug and Health Sciences University of Catania  Viale Andrea Doria 6 Catania I\u201095125 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Sodano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Napoli Federico II  Via Domenico Montesano 49 Napoli I\u201080131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-0841","authenticated-orcid":false,"given":"Ovidio","family":"Catanzano","sequence":"additional","affiliation":[{"name":"Institute for Polymers Composites and Biomaterials (IPCB)\u2013CNR  Via Campi Flegrei 34 Pozzuoli I\u201080078 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-5691","authenticated-orcid":false,"given":"Anna Di","family":"Porzio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Napoli Federico II  Via Domenico Montesano 49 Napoli I\u201080131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9192-7586","authenticated-orcid":false,"given":"Antonio","family":"Randazzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Napoli Federico II  Via Domenico Montesano 49 Napoli I\u201080131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2086-1276","authenticated-orcid":false,"given":"Salvatore","family":"Sortino","sequence":"additional","affiliation":[{"name":"PhotoChemLab Department of Drug and Health Sciences University of Catania  Viale Andrea Doria 6 Catania I\u201095125 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-0782","authenticated-orcid":false,"given":"Fabiana","family":"Quaglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Napoli Federico II  Via Domenico Montesano 49 Napoli I\u201080131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.05.068"},{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01038"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2011.03.019"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3773(19990712)38:13\/14<1882::AID-ANIE1882>3.0.CO;2-V"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2023.215052"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2021.09.003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(98)00092-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.1.355"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c02303"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr000040l"},{"key":"e_1_2_7_7_3","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.1c10964"},{"key":"e_1_2_7_7_4","doi-asserted-by":"publisher","DOI":"10.1039\/c2cs15272j"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9RA03840J"},{"key":"e_1_2_7_9_1","first-page":"190","volume":"32","author":"Xing H.","year":"2024","journal-title":"Bioact. 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