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The main symptoms of psoriasis include erythema, scales, itching, etc. At present, therapeutic drugs for psoriasis are continually evolving towards enhancing treatment efficacy and reducing side effects. Firstly, the pathogenesis and characteristics of psoriasis were summarized. Then, the types and benefits of topical therapy were introduced, such as the aspects of avoiding systemic toxic effects, first pass effect, and gastrointestinal reactions with accelerating the onset time of the drugs and improving its efficacy, and were compared to systemic drugs. In the case of methotrexate, cyclosporin A, Janus kinase (JAK) inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors, this review had a further discussion on the improvement and translation of these molecules from systemic therapy to topical therapy in clinical practice. To further augment the limitation of skin permeability, nanotechnology and novel topical drug delivery system including nanomedicines, hydrogels, ionic liquids, and microneedles were elaborated for psoriasis management. Also, exploration of topical targeting pathogenic genes through small interfering RNA (siRNA) using nanoparticles and ionic liquids (ILs) is of great significance for long-term treatment in psoriasis. Taken together, the development of numerous topical delivery platforms is expected to achieve enhanced penetration, and precise and efficient delivery of small molecule and RNA interference (RNAi) therapeutics in psoriasis with clinical translation prospects.<\/jats:p>","DOI":"10.3390\/pharmaceutics17030283","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T11:03:37Z","timestamp":1740049417000},"page":"283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Topical Therapy in Psoriasis: Clinical Benefits, Advances in Novel Drug Delivery Strategies, and Gene Therapy Regimen"],"prefix":"10.3390","volume":"17","author":[{"given":"Ying","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-8330","authenticated-orcid":false,"given":"Xiaonan","family":"Ma","sequence":"additional","affiliation":[{"name":"The Public Laboratory Platform of China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenduo","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-170X","authenticated-orcid":false,"given":"Yunfan","family":"Kong","sequence":"additional","affiliation":[{"name":"The F.M. Kirby Neurobiology Center, Boston Children\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5107-2416","authenticated-orcid":false,"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-0808","authenticated-orcid":false,"given":"Xiaofei","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China"},{"name":"NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41392-023-01655-6","article-title":"Signaling pathways and targeted therapies for psoriasis","volume":"8","author":"Guo","year":"2023","journal-title":"Signal Transduct. 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