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Despite advances in topical therapies, conventional formulations suffer from poor skin penetration, rapid clearance, local and systemic side effects, and suboptimal patient adherence. Polymeric nanogels, internally crosslinked three-dimensional polymer networks with dimensions of 10\u2013200 nm, emerged as promising platforms to overcome these limitations. Their unique properties including high water content, tunable porosity, biocompatibility, deformability, and stimulus-responsive behavior enhance skin penetration allowing for targeted therapeutic action. This review examines nanogel synthesis methods optimized for targeting skin inflammatory diseases, including biopolymer-based approaches utilizing chitosan and hyaluronic acid, offering insights into how different methods and advanced architecture provide multifunctional capacities and bioactivities. Translation challenges including manufacturing scalability, long-term safety assessment, and regulatory compliance are critically discussed alongside emerging opportunities in personalized medicine and smart microneedle integrated systems for adaptive therapy.<\/jats:p>","DOI":"10.3390\/gels12050354","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:04:59Z","timestamp":1776963899000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Polymeric Nanogels for Skin Applications"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8268-2137","authenticated-orcid":false,"given":"Sara","family":"Silva","sequence":"first","affiliation":[{"name":"Universidade Cat\u00f3lica Portuguesa, CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2014Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7705-2293","authenticated-orcid":false,"given":"Manuela","family":"Machado","sequence":"additional","affiliation":[{"name":"Universidade Cat\u00f3lica Portuguesa, CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2014Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3121-4514","authenticated-orcid":false,"given":"Eduardo M.","family":"Costa","sequence":"additional","affiliation":[{"name":"Universidade Cat\u00f3lica Portuguesa, CBQF\u2014Centro de Biotecnologia e Qu\u00edmica Fina\u2014Laborat\u00f3rio Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ujiie, H., Rosmarin, D., Sch\u00f6n, M.P., St\u00e4nder, S., Boch, K., Metz, M., Maurer, M., Thaci, D., Schmidt, E., and Cole, C. 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