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Therapeutic strategies that stimulate the resolution phase of inflammation have gained attention. Ac2\u201326, a mimetic peptide derived from annexin A1 (a pro\u2010resolving mediator), exhibits pro\u2010resolving and anti\u2010inflammatory properties, but its therapeutic potential is limited by poor aqueous solubility and rapid clearance. Here, we investigated whether Ac2\u201326 included in hydroxypropyl\u2010\u03b2\u2010cyclodextrin (CDX\u2010Ac2\u201326) enhances its pro\u2010resolving efficacy in an antigen\u2010induced arthritis model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Arthritic BALB\/c mice were treated with either free Ac2\u201326 or CDX\u2010Ac2\u201326 at doses 150, 50 and 15 \u03bcg per mouse (i.p.) at the peak of inflammation. Leukocyte recruitment, neutrophil apoptosis and efferocytosis were determined by cell morphology and flow cytometry. Cytokine levels were quantified by ELISA, mechanical hypernociception by electronic von Frey testing, and MerTK and CD47 expression were determined by flow cytometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>CDX\u2010Ac2\u201326 at a dose of 50 \u03bcg per mouse was sufficient to resolve inflammation, whereas free peptide required the highest dose to achieve similar effects. CDX\u2010Ac2\u201326 increased the expression of full\u2010length AnxA1, reduced accumulated neutrophils within the knee joint, decreased levels of CXCL1 and IL\u20101\u03b2 in periarticular tissues, improved histological outcomes, and alleviated pain. These effects were associated with enhanced apoptosis and MerTK\u2010mediated efferocytosis, along with decreased expression of CD47, a \u2018don\u2019t\u2010eat\u2010me\u2019 signal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Inclusion of Ac2\u201326 in cyclodextrin enhances its biological effects at lower doses and may represent a promising therapeutic strategy to promote inflammation resolution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70555","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:45:22Z","timestamp":1783057522000},"page":"5602-5620","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2\u2010Cyclodextrin inclusion enhances the pro\u2010resolving effects of the annexin A1 mimetic Ac2\u201326 in a mouse model 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