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However, the drug has a short residence time in the joint cavity, necessitating frequent administration, which results in poor patient compliance and limits its clinical use. To address these problems, dexamethasone sustained-release microspheres (Dex-MS-2) with single-phase zero-order release behavior were prepared using polymer blending combined with a release promoter. Their characteristics, in vitro release, and in vivo pharmacodynamics were evaluated. Dex-MS-2 had a slightly larger mean particle size than Dex-MS-1, but exhibited a narrower particle size distribution and good encapsulation efficiency. Compared with microspheres prepared by polymer blending alone (Dex-MS-1), the microspheres containing the release promoter exhibited no release lag and achieved zero-order release for 28 days. Following intra-articular injection in rats, Dex-MS-2 exhibited favorable anti-inflammatory activity and effectively inhibited joint swelling, with superior therapeutic efficacy to Dex-MS-1 and comparable efficacy to the marketed injection. The Dex-MS-2 developed in this study reduced the frequency of administration, improved patient compliance, and achieved sustained drug release. This formulation may effectively overcome the limitations associated with the marketed formulation.<\/jats:p>","DOI":"10.1021\/acsabm.6c01682","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:02:37Z","timestamp":1791212557000},"page":"9943-9957","source":"Crossref","is-referenced-by-count":0,"title":["Dexamethasone Sustained-Release Microspheres with Single-Phase Zero-Order Release Behavior for Intra-Articular Injection: Effects of Polymer Blending and Release Promoter Incorporation"],"prefix":"10.1021","volume":"9","author":[{"given":"Shiman","family":"Zhang","sequence":"first","affiliation":[{"name":"Shenyang Pharmaceutical University , , No. 103 Wenhua Road , ,","place":["Shenyang, China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuli","family":"Wang","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University , , No. 103 Wenhua Road , ,","place":["Shenyang, China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fucong","family":"Jia","sequence":"additional","affiliation":[{"name":"Wuya College of Innovation, Shenyang Pharmaceutical University , No. 103 Wenhua Road , ,","place":["Shenyang, China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University , , No. 103 Wenhua Road , ,","place":["Shenyang, China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University , , No. 103 Wenhua Road , ,","place":["Shenyang, China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8319-5151","authenticated-orcid":true,"given":"Xinggang","family":"Yang","sequence":"additional","affiliation":[{"name":"Shenyang Pharmaceutical University , , No. 103 Wenhua Road , ,","place":["Shenyang, China, 110016"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"8","key":"2026101904075200400_cit1","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1093\/gerona\/glw014","article-title":"Gender Differences in the Combined Effects of Cardiovascular Disease and Osteoarthritis on Progression to Functional Impairment in Older Mexican Americans","volume":"71","author":"Haan","year":"2016","journal-title":"J. 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