{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T21:00:07Z","timestamp":1785186007642,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173980"],"award-info":[{"award-number":["82173980"]}],"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":["81873017"],"award-info":[{"award-number":["81873017"]}],"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":["BK20211389"],"award-info":[{"award-number":["BK20211389"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017534","name":"Project 333 of Jiangsu Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017534","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010014","name":"Six Talent Peaks Project in Jiangsu Province","doi-asserted-by":"publisher","award":["YY\u2010028\u20102019"],"award-info":[{"award-number":["YY\u2010028\u20102019"]}],"id":[{"id":"10.13039\/501100010014","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sustainable retinal codelivery poses significant challenges technically, although it is imperative for synergistic treatment of wet age\u2010related macular degeneration (wAMD). Here, a microemulsion\u2010doped hydrogel (Bor\/PT\u2010M@TRG) is engineered as an intravitreal depot composing of temperature\u2010responsive hydrogel (TRG) and borneol\u2010decorated paeoniflorin (PF) &amp; tetramethylpyrazine (TMP)\u2010coloaded microemulsions (Bor\/PT\u2010M). Bor\/PT\u2010M@TRG, functioning as the \u201cammunition depot\u201d, resides in the vitreous and continuously releases Bor\/PT\u2010M as the therapeutic \u201cbullet\u201d, enabling deep penetration into the retina for 21 days. A single intravitreal injection of Bor\/PT\u2010M@TRG yields substantial reductions in choroidal neovascularization (CNV, a hallmark feature of wAMD) progression and mitigates oxidative stress\u2010induced damage in vivo. Combinational PF&amp;TMP regulates the \u201creactive oxygen species\/nuclear factor erythroid\u20102\u2010related factor 2\/heme oxygenase\u20101\u201d pathway and blocks the \u201chypoxia inducible factor\u20101\u03b1\/vascular endothelial growth factor\u201d signaling in retina, synergistically cutting off the loop of CNV formation. Utilizing fluorescence resonance energy transfer and liquid chromatography\u2010mass spectrometry techniques, they present compelling multifaceted evidence of sustainable retinal codelivery spanning formulations, ARPE\u201019 cells, in vivo eye balls, and ex vivo section\/retina\u2010choroid complex cell levels. Such codelivery approach is elucidated as the key driving force behind the exceptional therapeutic outcomes of Bor\/PT\u2010M@TRG. These findings highlight the significance of sustainable retinal drug codelivery and rational combination for effective treatment of wAMD.<\/jats:p>","DOI":"10.1002\/adhm.202303659","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T14:55:47Z","timestamp":1708613747000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Sustainable Retinal Drug Co\u2010Delivery for Boosting Therapeutic Efficacy in wAMD: Unveiling Multifaceted Evidence and Synergistic Mechanisms"],"prefix":"10.1002","volume":"13","author":[{"given":"Congyan","family":"Liu","sequence":"first","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenting","family":"Su","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Lv","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Kong","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Liu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Li","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese Medicine  155 Hanzhong Road Nanjing 210029 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1217-1865","authenticated-orcid":false,"given":"Ding","family":"Qu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Integrated Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"},{"name":"Jiangsu Provincial Academy of Traditional Chinese Medicine  100 Hongshan Road Nanjing 210028 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3]]},"reference":[{"key":"e_1_2_8_1_1","first-page":"31","volume":"7","author":"Fleckenstein M.","year":"2021","journal-title":"Nat. Rev."},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2102061"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-0696-3"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2022.101113"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113005"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.7150\/thno.42260"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmt.2023.101867"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100858"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c05447"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.10.022"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10040613"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-022-00554-w"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107792"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107452"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01829-y"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.01.080"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2022.102571"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.04.016"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202204994"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.05.035"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2020.07.031"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.10.036"},{"key":"e_1_2_8_14_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2019.07.082"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8BM00796A"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c07397"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120188"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.9b00717"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2018-0282"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.119361"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.7b00011"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2021.153822"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2022.120309"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aaw3423"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2020.1838116"},{"key":"e_1_2_8_21_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120600"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S51469"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11061133"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-02104-4"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.07.048"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/03639045.2021.1908331"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019102468"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14174"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10102635"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10121870"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.2c10506"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2016.10.008"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2019.05.065"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-00939-9"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202303659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T18:24:54Z","timestamp":1759775094000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202303659"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":48,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/adhm.202303659"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202303659","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-10-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2303659"}}