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Herein, SA\u2010loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA\u2010 loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L\u2010type hydrogels are found to have preferable drug penetration over D\u2010type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration.<\/jats:p>","DOI":"10.1002\/advs.202303495","type":"journal-article","created":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T05:14:47Z","timestamp":1701407687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Chiral Supramolecular Hydrogel Enhanced Transdermal Delivery of Sodium Aescinate to Modulate M1 Macrophage Polarization Against Lymphedema"],"prefix":"10.1002","volume":"11","author":[{"given":"Xueqian","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Lab of Metal Matrix Composites Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Materials Science and Engineering Shanghai Jiao Tong University  Shanghai 200240 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