{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:25:44Z","timestamp":1788531944054,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"publisher","award":["2022YFA1206000"],"award-info":[{"award-number":["2022YFA1206000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National key R & D program of Nanotechnology of China","award":["2020YFA0710700"],"award-info":[{"award-number":["2020YFA0710700"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32101068"],"award-info":[{"award-number":["32101068"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32101068"],"award-info":[{"award-number":["32101068"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Jiangsu Distinguished Professor Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Effective topical management of sensitive skin remains challenging because inadequate cutaneous delivery limits the therapeutic performance of many anti-inflammatory agents. Glycyrrhetinic acid (GA) possesses well-recognized anti-inflammatory and barrier-protective activities, yet its clinical potential is constrained by poor aqueous solubility and inefficient skin delivery. This study aimed to develop a hyaluronic acid (HA)-engineered ethosomal system to enhance the local delivery and therapeutic efficacy of GA for sensitive skin. Methods: HA-coated GA-loaded ethosomes (HAGA-ETs) were prepared by electrostatic adsorption of HA onto a cationic ethosomal template. The physicochemical properties, release behavior, storage stability, skin retention, cellular uptake, and biological activities of HAGA-ETs were systematically evaluated using TNF-\u03b1\/IFN-\u03b3-stimulated HaCaT cells and an SLS-induced 3D reconstructed skin model. Results: HAGA-ETs exhibited a mean particle size of 140.1 nm, encapsulation efficiency exceeding 95%, sustained drug release, and good storage stability. Compared with Free-GA and unmodified ethosomes, HAGA-ETs showed improved cytocompatibility, enhanced skin retention, greater keratinocyte uptake, and stronger anti-inflammatory activity. HA pre-saturation attenuated the enhanced cellular uptake of HAGA-ETs, supporting the involvement of HA receptor-mediated cellular interaction. HAGA-ETs also more effectively restored barrier-related markers, suppressed hyper-reactivity- and allergy-associated mediators, and inhibited the activation of MAPK\/NF-\u03baB, JAK1\/STAT1, and TRPV1-related signaling pathways in both cellular and 3D skin models. Conclusions: HA surface engineering effectively improved the topical delivery and local therapeutic efficacy of GA by enhancing skin retention and keratinocyte interaction. HAGA-ETs represent a promising nanoplatform for the local management of sensitive skin.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091114","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T13:50:44Z","timestamp":1788529844000},"page":"1114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Hyaluronic Acid-Coated Ethosomal Delivery System for Improving the Topical Delivery of Glycyrrhetinic Acid in Sensitive Skin"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2883-6531","authenticated-orcid":false,"given":"Yuling","family":"Wang","sequence":"first","affiliation":[{"name":"College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"},{"name":"Research and Development Center, Bloomage Biotechnology Corporation Limited, Jinan 250101, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Shujing","family":"Ren","sequence":"additional","affiliation":[{"name":"Research and Development Center, Bloomage Biotechnology Corporation Limited, Jinan 250101, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Jun","family":"Deng","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430075, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Dan","family":"Luo","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430075, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430075, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0061-8591","authenticated-orcid":false,"given":"Siyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Institute for Biomaterials, Tech Institute for Advanced Materials Bioinspired Biomedical Materials & Devices Center, College of Materials Science and Engineering, Jiangsu Collaborative Innovation Center for Advanced Inorganic Function Composites, Suqian Advanced Materials Industry Technology Innovation Center, Nanjing Tech University, Nanjing 211816, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8280-0030","authenticated-orcid":false,"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China"},{"name":"National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan 430075, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.2340\/00015555-2397","article-title":"Definition of sensitive skin: An expert position paper from the Special Interest Group on Sensitive Skin of the International Forum for the Study of Itch","volume":"97","author":"Misery","year":"2017","journal-title":"Acta Derm. 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