{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:16:16Z","timestamp":1788509776538,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"33","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1S10OD026764\u201001"],"award-info":[{"award-number":["1S10OD026764\u201001"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006770","name":"American Chemical Society Petroleum Research Fund","doi-asserted-by":"publisher","award":["69450\u2010DNI4"],"award-info":[{"award-number":["69450\u2010DNI4"]}],"id":[{"id":"10.13039\/100006770","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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hydrophilic small\u2010molecule therapeutics are difficult to encapsulate using conventional depot delivery systems because of their high\u2010water solubility and rapid diffusion. Here we report a drug\u2010interactive peptide coacervate platform for sustained release of tetrodotoxin (TTX), a potent site\u20101 sodium channel blocker used for local anesthesia. We discovered that a mussel foot protein\u2010inspired peptide (Mfp3s\u2010pep) interacts with TTX and undergoes spontaneous self\u2010coacervation under physiological conditions, forming dynamic assemblies that encapsulate TTX via multivalent noncovalent interactions. The Mfp3s\u2010pep coacervates sequester 29% of TTX and significantly prolong its release. In a rat sciatic nerve block model, the TTX\u2010Mfp3s\u2010pep formulation extended sensory blockade up to 10.5\u00a0h and reduced systemic toxicity by 1.5\u2010fold, which had not been achievable with TTX alone without drug synergy. Molecular docking and molecular dynamics simulations further reveal that coacervate structures stabilize TTX through a dynamic hydrogen\u2010bonding network and multivalent interactions. This work establishes peptide coacervates as a potential platform for delivery of hydrophilic therapeutics.<\/jats:p>","DOI":"10.1002\/adhm.71514","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:04:16Z","timestamp":1785819856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peptide Coacervates as Dynamic and Interactive Depots for Tetrodotoxin in Long\u2010Acting Local Anesthesia"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6080-4540","authenticated-orcid":false,"given":"Xing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5536-925X","authenticated-orcid":false,"given":"Jiahao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2656-4644","authenticated-orcid":false,"given":"Wanqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9405-6098","authenticated-orcid":false,"given":"Zeyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8643-7059","authenticated-orcid":false,"given":"Zufeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Biology Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9321-6411","authenticated-orcid":false,"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6072-7533","authenticated-orcid":false,"given":"Zhicheng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Chemistry Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202520727"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.9b00432"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010021\u201000793\u2010y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2025.07.006"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.4c01004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202400265"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202211550"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202206643"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202511230"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2523195123"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau2486"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00437"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201010296\u20109"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202406158"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202503872"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c09484"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201809587"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201037563\u20100"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202502205"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202501542"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/la504316q"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsusc.2020.145589"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biomac.4c01506"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201027463\u20106"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/polb.22256"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010024\u201001254\u2010y"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.5c09726"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010022\u201000505\u20104"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557\u2010021\u201000854\u20104"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121708"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.1100365"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201600210"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202420399"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.114023"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.3c00689"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202410566"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/d4sm01477d"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c17880"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/pola.28368"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010199807000\u201000019"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/d2cs00133k"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1cs00838b"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6c06972"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.7b02461"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1113\/jp286538"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201102494"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201604155"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201037963\u20102"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010026\u201069184\u20108"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.2000.61.133"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.068643"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201037002\u20100"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13020\u2010025\u201001185\u2010z"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00119.2006"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbaexp.2007.08.004"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140062"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201041946\u20108"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.140873"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.127496"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12649\u2010025\u201003430\u2010w"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2018.06.015"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.4411241"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010026\u201072967\u20108"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c07748"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.71514","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.71514","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.71514","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:50:00Z","timestamp":1788508200000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.71514"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":64,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/adhm.71514"],"URL":"https:\/\/doi.org\/10.1002\/adhm.71514","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]},"assertion":[{"value":"2026-05-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71514"}}