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Instillation of antibiotic eyedrops is the most common management of bacterial keratitis but usually suffers from low bioavailability (i.e., &lt;5%) and frequent administration, due to the existence of corneal epithelial barrier that prevents large and hydrophilic drug molecules from entering the cornea, and the tear film on corneal surface that rapidly washes drug away from the cornea. Here, a self\u2010implantable core\u2013shell microneedle (MN) patch with programmed drug release property to facilitate bacterial keratitis treatment is reported. The pH\u2010responsive antimicrobial nanoparticles (NPs), Ag@ZIF\u20108, which are capable of producing antibacterial metal ions in the infected cornea and generating oxidative stress in bacteria, are loaded in the dissolvable core, while the anti\u2010angiogenic drug, rapamycin (Rapa), is encapsulated in the biodegradable shell, thereby enabling rapid release of Ag@ZIF\u20108 NPs and sustained release of Rapa after corneal insertion. Owing to the programmed release feature, one single administration of the core\u2013shell MN patch in a rat model of bacterial keratitis, can achieve satisfactory antimicrobial activity and superior anti\u2010angiogenic and anti\u2010inflammation effects as compared to daily topical eyedrops, indicating a great potential for the infectious keratitis therapy in clinics.<\/jats:p>","DOI":"10.1002\/smll.202310461","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T03:55:34Z","timestamp":1708746934000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Self\u2010Implantable Core\u2013Shell Microneedle Patch for Long\u2010Acting Treatment of Keratitis via Programmed Drug Release"],"prefix":"10.1002","volume":"20","author":[{"given":"Xue","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinli","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongnian","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering The City University of Hong Kong  Kowloon Hong Kong SAR 999077 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-7267","authenticated-orcid":false,"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  Wuhan 430071 China"},{"name":"TaiKang Center for Life and Medical Sciences Wuhan University  Wuhan 430071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,23]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"376","volume":"38","author":"Polat H. 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