{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:08:26Z","timestamp":1785413306013,"version":"3.56.0"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173982"],"award-info":[{"award-number":["82173982"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82173982"],"award-info":[{"award-number":["82173982"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangdong Natural Science Project","award":["2022A1515011382"],"award-info":[{"award-number":["2022A1515011382"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Shikonin (SKN) is a potential anti-psoriatic agent, yet its clinical application is hindered by poor water solubility and low stratum corneum permeability. This study aimed to develop a reactive oxygen species (ROS)-responsive hydrogel microneedle system encapsulating SKN-loaded polymeric micelles (SKN-M@MN) to enhance transdermal delivery and evaluate its therapeutic effects in psoriasis. Methods: Shikonin-loaded micelles (SKN-M) were optimised using a thin-film hydration method. SKN-M@MN was fabricated via a two-step casting method using phenylboronic acid-modified hyaluronic acid (HA-PBA) and polyvinylpyrrolidone K90 as the tip matrix. Skin penetration, ROS-responsive release, and anti-psoriatic efficacy were assessed in an imiquimod (IMQ)-induced mouse model. Mechanistic studies included RNA-seq, qPCR, and Western blotting. Results: SKN-M achieved an encapsulation efficiency of 93.45 \u00b1 0.24%, a particle size of 62.49 \u00b1 0.92 nm, and a zeta potential of \u221236.78 \u00b1 1.12 mV. SKN-M@MN showed 100% skin penetration, sustained drug release, and accelerated degradation under high ROS conditions. In psoriatic mice, SKN-M@MN significantly alleviated skin lesions, reduced epidermal hyperplasia (Ki67), and downregulated IL-17A and TNF-\u03b1 levels both locally and systemically. Mechanistically, it inhibited the PI3K\/AKT and NF-\u03baB signalling pathways. Conclusions: The SKN-M@MN microneedle platform integrates physical skin penetration, ROS-responsive drug release, and pathway inhibition, offering an effective strategy for transdermal delivery of poorly soluble drugs in psoriasis therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080939","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:54Z","timestamp":1785411534000},"page":"939","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shikonin-Loaded ROS-Responsive Microneedles for Psoriasis Therapy: Formulation, Transdermal Delivery, and Mechanistic Evaluation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0105-5337","authenticated-orcid":false,"given":"Haoran","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqin","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Zhuang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huishan","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxian","family":"Ou","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dasc\u0103lu, R.C., B\u0103rbulescu, A.L., Stoica, L.E., Dinescu, \u0218.C., Bi\u021b\u0103, C.E., Popoviciu, H.V., Ionescu, R.A., and Vreju, F.A. 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