{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T22:33:41Z","timestamp":1788820421904,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Pharmaceutical University Shenzhen Hospital (Longgang)","award":["202410573006"],"award-info":[{"award-number":["202410573006"]}]},{"name":"Guangdong Pharmaceutical University Joint Fund (Joint Fund for Institutions)","award":["202410573006"],"award-info":[{"award-number":["202410573006"]}]},{"name":"Provincial university Students\u2019 innovation and entrepreneurship training programs in 2024","award":["202410573006"],"award-info":[{"award-number":["202410573006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Indomethacin (IDM) is commonly used to treat chronic inflammatory diseases such as rheumatoid arthritis and osteoarthritis. However, long-term oral IDM treatment can harm the gastrointestinal tract. This study presents a design for encapsulating IDM within mixed micelles (MMs)-loaded dissolving microneedles (DMNs) to improve and sustain transdermal drug delivery. Methods: Indomethacin-loaded mixed micelles (IDM-MMs) were prepared from Soluplus\u00ae and Poloxamer F127 by means of a thin-film hydration method. The MMs-loaded DMNs were fabricated using a two-step molding method and evaluated for storage stability, insertion ability, in vitro release, in vitro transdermal penetration, and in vivo PK\/PD studies. Results: The obtained MMs were stable at 4 \u00b0C and 30 \u00b0C for 60 days. The in vitro IDM transdermal penetration was remarkably improved by the MMs-loaded DMNs compared to a commercial patch. A pharmacokinetic study demonstrated that the MMs-loaded DMNs had a relative bioavailability of 4.1 in comparison with the commercial patch. Furthermore, the MMs-loaded DMNs showed a significantly shorter lag time than the commercial patch, as well as a more stable plasma concentration than the DMNs without MMs. The therapeutic efficacy of the IDM DMNs was examined in Complete Freund\u2019s Adjuvant-induced arthritis mice. The IDM DMN treatment effectively reduced arthritis severity, resulting in decreased paw swelling, arthritis index, spleen hyperplasia, and serum IL-1\u03b2 and TNF-\u03b1 levels. Conclusions: Our findings demonstrated that the novel MMs-loaded DMNs were an effective strategy for sustained IDM release, providing an alternate route of anti-inflammatory drug delivery.<\/jats:p>","DOI":"10.3390\/pharmaceutics16121505","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T10:17:23Z","timestamp":1732270643000},"page":"1505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Preparation and In Vitro\/In Vivo Characterization of Mixed-Micelles-Loaded Dissolving Microneedles for Sustained Release of Indomethacin"],"prefix":"10.3390","volume":"16","author":[{"given":"Baojie","family":"Wang","sequence":"first","affiliation":[{"name":"The Third People\u2019s Hospital of Longgang District, Shenzhen 518112, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Langkun","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 East Waihuan Road, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 East Waihuan Road, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 East Waihuan Road, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, 280 East Waihuan Road, Guangzhou 510006, China"},{"name":"Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s00535-019-01657-8","article-title":"Current knowledge on non-steroidal anti-inflammatory drug-induced small-bowel damage: A comprehensive review","volume":"55","author":"Watanabe","year":"2020","journal-title":"J. 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