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Although developing a slow\u2010releasing dexmedetomidine formulation is a conventional strategy to address these problems, it is unfortunately limited by the small molecule and high solubility of the drug. In this study, we designed a self\u2010assembling peptide (SAP)\u00a0by referring to the chemical structure of dexmedetomidine, which contains a pH\u2010responsive imidazole group and a hydrophobic benzene group. By also containing the two groups, the peptide could simultaneously undergo pH\u2010induced phase\u2010transition together with dexmedetomidine, leading to their co\u2010assembly to form drug\u2013peptide complexes. Different from well\u2010ordered nanofibers formed by the peptide alone, the co\u2010assembly system formed nanoparticles with relatively disordered core structures like biomolecular condensates. In this manner, the obtained formulation exhibited high drug encapsulation efficiency and a slow\u2010releasing profile, which further alleviated hypotension and extended the duration of sedative and analgesic efficacy in animal models. This study proposed a promising strategy to design SAPs for drug delivery in a personalized way. It also provided the slow\u2010releasing dexmedetomidine formulation as a promising candidate for clinical application.<\/jats:p>","DOI":"10.1002\/chem.202503614","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T09:10:46Z","timestamp":1775812246000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synchronized Phase\u2010Transition\u2010Induced Co\u2010Assembly of Short Peptide and Dexmedetomidine for Efficient Drug Encapsulation and Slow Release"],"prefix":"10.1002","volume":"32","author":[{"given":"Xiaoyu","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Anesthesiology West China Hospital Sichuan University  Chengdu China"},{"name":"Laboratory of Anesthesia and Critical Care Medicine National\u2010Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology West China Hospital Sichuan University  Chengdu 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