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Here, we developed a hyaluronic acid (HA)\u2010coated MEL\u2010based polymersome (PMHA) for CD44\u2010targeted codelivery of MEL and celecoxib (CXB). MEL was incorporated into the vesicular membrane, whereas CXB was loaded into the hydrophobic domain. PMHA showed a hydrodynamic diameter of 265.5\u2009\u00b1\u20091.6\u2009nm, a zeta\u2010potential of \u221221.14\u2009\u00b1\u20091.1\u2009mV, a CXB encapsulation efficiency of 70.81\u2009\u00b1\u20094.18%, and a drug loading capacity of 12.87\u2009\u00b1\u20091.92%. In lipopolysaccharide (LPS)\u2010stimulated RAW 264.7 macrophages, anti\u2010CD44 antibody blocking reduced Alexa Fluor 647\u2010labeled PMHA uptake by approximately 37.5%, supporting HA\u2013CD44\u2010mediated internalization. PMHA reduced MEL\u2010associated cytotoxicity and hemolytic activity and enabled pH\u2010responsive CXB release. Codelivery of MEL and CXB suppressed cyclooxygenase\u20102\u2009(COX\u20102) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) expression, with combination index (CI) values of 0.48 and 0.67, respectively. These findings support further evaluation of PMHA as a macrophage\u2010targeted anti\u2010inflammatory nanoplatform.<\/jats:p>","DOI":"10.1002\/cmdc.70396","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:41:26Z","timestamp":1784857286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD44\u2010Targeted Delivery of Melittin and Celecoxib via Hyaluronic Acid\u2010Coated Polymersomes for Synergistic Anti\u2010Inflammatory Therapy"],"prefix":"10.1002","volume":"21","author":[{"given":"Youngheun","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering Sogang University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering Sogang University  Seoul Republic of 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