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However, delivering immunosuppressive drugs to the lacrimal glands for SSDE therapy safely and sustainably poses significant challenges in clinical practice. Herein, a ROS\u2010responsive microneedle patch with detachable functionality (CE\u2010MN) is developed to enable straightforward and minimally invasive administration to the lacrimal gland area by penetrating the periocular skin. CE\u2010MN is loaded with immunosuppressive cyclosporin A and anti\u2010inflammatory drug epigallocatechin gallate, the latter also serving as a cross\u2010linker for the microneedle matrix. Poly(N\u2010isopropylacrylamide\u2010co\u2010butylacrylate), a temperature\u2010sensitive polymer is utilized to fabricate separable layers that allow controlled detachment of the base from the needle, reducing patient discomfort. CE\u2010MN is capable of modulating drug release by responding to ROS, facilitating on\u2010demand release, and drug accumulation to the lacrimal gland. Compared to traditional eye drops, the CE\u2010MN patch facilitated long\u2010acting drug delivery to the lacrimal gland for more than 48\u00a0h, demonstrating potent anti\u2010inflammatory and immunosuppressive effects in an SSDE mouse model by scavenging ROS and inhibiting the proliferation of Th1, Th17 cells, and macrophages. Overall, this long\u2010acting microneedle patch potentially offers a novel clinical approach for treating SSDE and other ocular chronic diseases.<\/jats:p>","DOI":"10.1002\/advs.202409562","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T13:11:28Z","timestamp":1736514688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["ROS\u2010Responsive Microneedle Patches Enable Peri\u2010Lacrimal Gland Therapeutic Administration for Long\u2010Acting Therapy of Sj\u00f6gren's Syndrome\u2010Related Dry Eye"],"prefix":"10.1002","volume":"12","author":[{"given":"Jingqing","family":"Mu","sequence":"first","affiliation":[{"name":"Aier Eye Hospital Tianjin University  Fukang Road Tianjin 300110 China"},{"name":"Changsha Aier Eye Hospital  Changsha Hunan 410015 China"},{"name":"Aier Eye Institute  Changsha Hunan 410009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Ding","sequence":"additional","affiliation":[{"name":"Aier Academy of Ophthalmology Central South University  Changsha Hunan 410125 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yapeng","family":"Song","sequence":"additional","affiliation":[{"name":"Key Laboratory of Functional Polymer Materials of Ministry of Education State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for New Organic Matter College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoyue","family":"Mi","sequence":"additional","affiliation":[{"name":"Aier Eye Hospital Tianjin University  Fukang Road Tianjin 300110 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Fang","sequence":"additional","affiliation":[{"name":"Aier Eye Hospital Tianjin University  Fukang Road Tianjin 300110 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baihua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Second Xiangya Hospital Central South University  Changsha Hunan 410011 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yao","sequence":"additional","affiliation":[{"name":"Academy of Medical Engineering &amp; Translational Medicine, Medical College Tianjin University  Tianjin 300072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuguang","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Institute of Ophthalmology Beijing Tongren Eye Center Beijing Key Laboratory of Ophthalmology and Visual Sciences Beijing Tongren Hospital Capital Medical University  Beijing 100005 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Ophthalmology and Visual Science Tianjin Eye Institute Tianjin Eye Hospital  Tianjin 300020 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0916-7451","authenticated-orcid":false,"given":"Shutao","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Functional Polymer Materials of Ministry of Education State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for New Organic Matter College of Chemistry Nankai University  Tianjin 300071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Hua","sequence":"additional","affiliation":[{"name":"Aier Eye Hospital Tianjin University  Fukang Road Tianjin 300110 China"},{"name":"Changsha Aier Eye Hospital  Changsha Hunan 410015 China"},{"name":"Aier Eye Institute  Changsha Hunan 410009 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1177\/11206721221091375"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11102809"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072299"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-23651"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-022-00551-6"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10325"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S279051"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2020.1757121"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1BM01453F"},{"key":"e_1_2_8_7_1","first-page":"47","volume":"2","author":"Cholkar K.","year":"2015","journal-title":"J. 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