{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T19:30:10Z","timestamp":1770751810419,"version":"3.50.0"},"reference-count":68,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P."},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Applied Sciences"],"abstract":"<jats:p>Skin pigmentation results from the melanin production by melanocytes, an essential process for protection against ultraviolet radiation and for maintaining cutaneous homeostasis. Disruptions in this balance lead to pigmentary disorders, such as hyperpigmentation, which is characterized by localized or diffuse darkening of the skin. Its most prevalent forms include melasma, post-inflammatory hyperpigmentation, and solar lentigines, often driven by hormonal, inflammatory, and environmental factors, particularly sun exposure. Despite being clinically benign, these conditions have a significant impact on self-esteem and quality of life. Conventional treatments rely on depigmenting agents such as hydroquinone, retinoids, and corticosteroids, as well as chemical peels, and laser or light-based therapies, frequently used in combination. However, limited efficacy, prolonged treatment durations, and potential adverse effects underscore the need for safer and more effective alternatives. In recent years, research has focused on developing novel approaches, with nanotechnology-based delivery systems and minimally invasive techniques, such as microneedling, standing out as particularly promising fields. In parallel, the growing number of interventional clinical trials reflects an increasing interest in optimizing topical depigmenting strategies. This review summarizes the main types of hyperpigmentation, the depigmenting substances currently used, and emerging therapeutic approaches with potential clinical impact.<\/jats:p>","DOI":"10.3390\/app16041735","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T11:16:38Z","timestamp":1770722198000},"page":"1735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Innovative Skin Depigmenting Strategies: A Review"],"prefix":"10.3390","volume":"16","author":[{"given":"Rita","family":"Carneiro","sequence":"first","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5080-032X","authenticated-orcid":false,"given":"Carla M.","family":"Lopes","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"FP-BHS\u2014Biomedical and Health Sciences Research Unit, FFP-I3ID\u2014Instituto de Investiga\u00e7\u00e3o, Inova\u00e7\u00e3o e Desenvolvimento, Faculdade Ci\u00eancias da Sa\u00fade, Universidade Fernando Pessoa, Rua Carlos da Maia 296, 4200-150 Porto, Portugal"},{"name":"RISE\u2014Health Research Network: From the Lab to the Community, Faculty of Medicine, University of Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-3366","authenticated-orcid":false,"given":"Maria Helena","family":"Amaral","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jin, R., Luo, L., and Zheng, J. 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