{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:20:11Z","timestamp":1787138411359,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"58","license":[{"start":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T00:00:00Z","timestamp":1757721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA0919100"],"award-info":[{"award-number":["2024YFA0919100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2322011"],"award-info":[{"award-number":["T2322011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52273207"],"award-info":[{"award-number":["52273207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22278214"],"award-info":[{"award-number":["22278214"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20231273"],"award-info":[{"award-number":["BK20231273"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2025,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Plant\u2010derived nanovesicles offer promising potential for transdermal drug delivery due to their inherent biocompatibility and low immunogenicity, yet face limitations in drug loading, structural stability, and functional optimization. This study presents a versatile Hybrid\u2010Gel platform that integrates CoQ10\u2010loaded hybrid vesicles with an injectable, pH\u2010responsive hydrogel to enhance localized drug delivery. High\u2010purity nanovesicles are isolated using an optimized ultracentrifugation (UC) and size\u2010exclusion chromatography (SEC) method, then hybridized with liposomes to improve encapsulation and skin penetration. To further optimize localized delivery performance, an injectable binary hydrogel system is then introduced. This hydrogel, formed via Schiff base crosslinking between hyperbranched polyethylene glycol and aldehyde\u2010modified hyaluronic acid (A\u2010HA), exhibits mild gelation conditions, excellent injectability, and strong tissue adhesion. The hydrogel effectively encapsulates hybrid nanovesicles, ensuring enhanced stability, ease of administration, and controlled, pH\u2010responsive release. As a proof of concept, an in vitro permeation test with porcine skin model demonstrates that the hydrogel significantly improves CoQ10 penetration, achieving a more than fourfold increase in transdermal efficiency compared to free CoQ10, suggesting superior bioavailability. This synergistic approach, combining hybrid nanovesicle\u2010mediated drug transport with a dynamic hydrogel matrix, offers a robust and versatile platform for localized transdermal therapy, with potential applications in precision medicine, regenerative treatments, and chronic disease management.<\/jats:p>","DOI":"10.1002\/chem.202501465","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T12:25:40Z","timestamp":1757766340000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Injectable Hyaluronic Acid Hydrogel Integrated with Hybrid Nanovesicles for Synergistic Enhancement of Transdermal Drug Delivery"],"prefix":"10.1002","volume":"31","author":[{"given":"Guilong","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwei","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingdong","family":"Cheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510655 China"},{"name":"Biomedical Innovation Center, The Sixth Affiliated Hospital Sun Yat\u2010sen University  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4420-5836","authenticated-orcid":false,"given":"Ziyi","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Materials\u2010Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University  30 Puzhu South Road Nanjing 211816 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,13]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1504"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36581-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202110746"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.09.025"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.03.007"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.08.016"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202306721"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.02.035"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2024.106365"},{"key":"e_1_2_7_10_1","first-page":"3879","volume-title":"Plant exosome nanovesicles (PENs): green delivery platforms","author":"Cao M.","year":"2023"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2020241118"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.586130"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4NA00501E"},{"key":"e_1_2_7_14_1","first-page":"565","volume-title":"Highly effective detection of exosomal miRNAs in plasma using liposome\u2010mediated transfection CRISPR\/Cas13a","author":"Zhang J.","year":"2023"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.12.027"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202106682"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202302626"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2017.41"},{"key":"e_1_2_7_19_1","volume":"10","author":"Zhang K.","year":"2018","journal-title":"ACS Appl. Mater. Inter."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.04.041"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2024.2337255"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202201105"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep21933"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01264-5"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b18927"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.04.003"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.05.020"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201910282"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201500556"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/marc.202500310"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.macromol.1c00537"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmt.2018.06.008"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.03.008"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/macp.202200348"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c01370"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/admi.202300262"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cej.2021.130610"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.1c02141"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2020.116922"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201505336"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202402836"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.4c05523"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202501465","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T05:58:45Z","timestamp":1760680725000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.202501465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,13]]},"references-count":42,"journal-issue":{"issue":"58","published-print":{"date-parts":[[2025,10,16]]}},"alternative-id":["10.1002\/chem.202501465"],"URL":"https:\/\/doi.org\/10.1002\/chem.202501465","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,13]]},"assertion":[{"value":"2025-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01465"}}