{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T10:28:04Z","timestamp":1777544884505,"version":"3.51.4"},"reference-count":90,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T00:00:00Z","timestamp":1764374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["SAF2016-80427-R"],"award-info":[{"award-number":["SAF2016-80427-R"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["PID2019-108806RB-I00"],"award-info":[{"award-number":["PID2019-108806RB-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTC-2017-6465-1"],"award-info":[{"award-number":["RTC-2017-6465-1"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["DI-14-06926"],"award-info":[{"award-number":["DI-14-06926"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017325","name":"Engineering Research Centers","doi-asserted-by":"publisher","award":["2022-POC1"],"award-info":[{"award-number":["2022-POC1"]}],"id":[{"id":"10.13039\/100017325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014849","name":"Valencia Department of Education Culture and Sport","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014849","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017167","name":"International Centre for Theoretical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017167","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["CIPROM\/2023\/053"],"award-info":[{"award-number":["CIPROM\/2023\/053"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["BEFPI\/2018\/055"],"award-info":[{"award-number":["BEFPI\/2018\/055"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003359","name":"Generalitat Valenciana","doi-asserted-by":"publisher","award":["ACIF-2016-021"],"award-info":[{"award-number":["ACIF-2016-021"]}],"id":[{"id":"10.13039\/501100003359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ERC-CoG-2014-648831"],"award-info":[{"award-number":["ERC-CoG-2014-648831"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Spanish Association Against Cancer Scientific Foundation","doi-asserted-by":"publisher","award":["INVES211323CONE"],"award-info":[{"award-number":["INVES211323CONE"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016028","name":"Valencia Innovation Agency","doi-asserted-by":"publisher","award":["L.T-C INNTAL31\/19\/005"],"award-info":[{"award-number":["L.T-C INNTAL31\/19\/005"]}],"id":[{"id":"10.13039\/501100016028","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomaterials"],"published-print":{"date-parts":[[2026,5]]},"DOI":"10.1016\/j.biomaterials.2025.123867","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T07:51:52Z","timestamp":1764229912000},"page":"123867","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["A rationally designed polypeptide-based hybrid platform for targeted intranasal brain drug delivery"],"prefix":"10.1016","volume":"328","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4196-0855","authenticated-orcid":false,"given":"Inmaculada","family":"Conejos-S\u00e1nchez","sequence":"first","affiliation":[]},{"given":"Tetiana","family":"Melnyk","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2293-0359","authenticated-orcid":false,"given":"Esther","family":"Masi\u00e1","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Morell\u00f3-Bolumar","sequence":"additional","affiliation":[]},{"given":"Luz","family":"Tortajada-Comeche","sequence":"additional","affiliation":[]},{"given":"Irene","family":"Dolz-P\u00e9rez","sequence":"additional","affiliation":[]},{"given":"Luc\u00eda In\u00e9s","family":"Torrijos-Saiz","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Tenhaeff","sequence":"additional","affiliation":[]},{"given":"Julia","family":"Roosz","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5334-6641","authenticated-orcid":false,"given":"Alessia","family":"Moruzzi","sequence":"additional","affiliation":[]},{"given":"Gloria","family":"Sogorb","sequence":"additional","affiliation":[]},{"given":"Maria","family":"Medel","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-0581","authenticated-orcid":false,"given":"Peter","family":"Loskill","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1079-935X","authenticated-orcid":false,"given":"Esther","family":"Rosell\u00f3","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6873-5244","authenticated-orcid":false,"given":"Victor","family":"Sebastian","sequence":"additional","affiliation":[]},{"given":"Helena","family":"Florindo","sequence":"additional","affiliation":[]},{"given":"Carles","family":"Felip-Le\u00f3n","sequence":"additional","affiliation":[]},{"given":"Vicent J.","family":"Nebot","sequence":"additional","affiliation":[]},{"given":"Vicente","family":"Herranz-P\u00e9rez","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Manuel","family":"Garc\u00eda-Vedugo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7771-3373","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Vicent","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"key":"10.1016\/j.biomaterials.2025.123867_bib1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S1474-4422(24)00038-3","article-title":"Global, regional, and national burden of disorders affecting the nervous system, 1990\u20132021: a systematic analysis for the global burden of disease study 2021","volume":"23","author":"Steinmetz","year":"2024","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib2","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000205009","article-title":"Projected global burden of brain disorders through 2050 (P7-15.001)","volume":"102","author":"Lei","year":"2024","journal-title":"Neurology"},{"key":"10.1016\/j.biomaterials.2025.123867_bib3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41392-023-01481-w","article-title":"The blood\u2013brain barrier: structure, regulation and drug delivery","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct. Targeted Ther."},{"key":"10.1016\/j.biomaterials.2025.123867_bib4","doi-asserted-by":"crossref","first-page":"566","DOI":"10.2174\/156720112803529828","article-title":"Anatomical and histological factors affecting intranasal drug and vaccine delivery","volume":"9","author":"Gizurarson","year":"2012","journal-title":"Curr. Drug Deliv."},{"key":"10.1016\/j.biomaterials.2025.123867_bib5","article-title":"On a highway to the brain: a review on nose-to-brain drug delivery using nanoparticles","volume":"29","author":"Formica","year":"2022","journal-title":"Appl. Mater. Today"},{"key":"10.1016\/j.biomaterials.2025.123867_bib6","doi-asserted-by":"crossref","DOI":"10.1002\/wnan.1532","article-title":"Envisioning the future of polymer therapeutics for brain disorders","volume":"11","author":"Rodriguez-Otormin","year":"2019","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s40005-022-00589-5","article-title":"Drug delivery to the brain via the nasal route of administration: exploration of key targets and major consideration factors","volume":"53","author":"Jeong","year":"2023","journal-title":"J. Pharm. Investig."},{"key":"10.1016\/j.biomaterials.2025.123867_bib8","doi-asserted-by":"crossref","DOI":"10.3389\/fddev.2023.1247162","article-title":"Transnasal-brain delivery of nanomedicines for neurodegenerative diseases","volume":"3","author":"Zhang","year":"2023","journal-title":"Front. Drug Delivery"},{"key":"10.1016\/j.biomaterials.2025.123867_bib9","doi-asserted-by":"crossref","first-page":"615","DOI":"10.3390\/ph18050615","article-title":"Advancements in nanocarrier systems for nose-to-brain drug delivery","volume":"18","author":"Nguyen","year":"2025","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.biomaterials.2025.123867_bib10","doi-asserted-by":"crossref","first-page":"4857","DOI":"10.2147\/IJN.S454553","article-title":"Brain targeting nanomedicines: pitfalls and promise","volume":"19","author":"Kakinen","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.biomaterials.2025.123867_bib11","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/17425247.2025.2464714","article-title":"Bringing intranasal drug delivery for malignancies in the brain to market","volume":"22","author":"Chen","year":"2025","journal-title":"Expet Opin. Drug Deliv."},{"key":"10.1016\/j.biomaterials.2025.123867_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.addr.2020.10.007","article-title":"Therapeutic potential of polypeptide-based conjugates: rational design and analytical tools that can boost clinical translation","volume":"160","author":"Melnyk","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.biomaterials.2025.123867_bib13","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202300309RR","article-title":"Elastin\u2010like polypeptide delivery of anti\u2010inflammatory peptides to the brain following ischemic stroke","volume":"37","author":"Howell","year":"2023","journal-title":"FASEB J."},{"key":"10.1016\/j.biomaterials.2025.123867_bib14","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1080\/00914037.2024.2443165","article-title":"Optimizing nasal drug delivery for peptides, proteins, and small molecules: strategic use of materials and techniques to target the CNS","volume":"74","author":"Mittal","year":"2025","journal-title":"Int. J. Polym. Mater. Polym. Biomater."},{"key":"10.1016\/j.biomaterials.2025.123867_bib15","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.3390\/ijms24043390","article-title":"Biomaterials-enhanced intranasal delivery of drugs as a direct route for brain targeting","volume":"24","author":"Marcello","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.biomaterials.2025.123867_bib16","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.1016\/j.bmc.2017.11.001","article-title":"Nose-to-brain peptide delivery \u2013 the potential of nanotechnology","volume":"26","author":"Samaridou","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.biomaterials.2025.123867_bib17","article-title":"Fabrication of active targeting lipid nanoparticles: challenges and perspectives","volume":"16","author":"Menon","year":"2022","journal-title":"Mater. Today Adv."},{"key":"10.1016\/j.biomaterials.2025.123867_bib18","doi-asserted-by":"crossref","DOI":"10.1002\/adma.201702888","article-title":"Nanocarriers: capturing \u201cextraordinary\u201d soft-assembled charge-like polypeptides as a strategy for nanocarrier design (Adv. Mater. 39\/2017)","volume":"29","author":"Duro-Castano","year":"2017","journal-title":"Adv. Mater."},{"key":"10.1016\/j.biomaterials.2025.123867_bib19","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/s41565-019-0567-y","article-title":"Smart cancer nanomedicine","volume":"14","author":"van der Meel","year":"2019","journal-title":"Nat. Nanotechnol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib20","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.jconrel.2011.12.021","article-title":"Administration, distribution, metabolism and elimination of polymer therapeutics","volume":"161","author":"Markovsky","year":"2012","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.biomaterials.2025.123867_bib21","doi-asserted-by":"crossref","DOI":"10.1038\/s44222-025-00306-5","article-title":"The emerging era of structural nanomedicine","author":"Mirkin","year":"2025","journal-title":"Nat. Rev. Bioeng."},{"key":"10.1016\/j.biomaterials.2025.123867_bib22","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1021\/acs.molpharmaceut.5b00358","article-title":"Well-defined star-shaped polyglutamates with improved pharmacokinetic profiles as excellent candidates for biomedical applications","volume":"12","author":"Duro-Castano","year":"2015","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.biomaterials.2025.123867_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2024.123922","article-title":"An overview of in vitro and in vivo techniques for characterization of intranasal protein and peptide formulations for brain targeting","volume":"654","author":"Wong","year":"2024","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.biomaterials.2025.123867_bib24","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1021\/mp300495e","article-title":"Diffusion of macromolecules in the brain: implications for drug delivery","volume":"10","author":"Wolak","year":"2013","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.biomaterials.2025.123867_bib25","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s11095-022-03222-0","article-title":"Effect of particle size and surface charge on nanoparticles diffusion in the brain white matter","volume":"39","author":"Yuan","year":"2022","journal-title":"Pharm. Res."},{"key":"10.1016\/j.biomaterials.2025.123867_bib26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.csbj.2024.06.002","article-title":"Numerical simulation study of nanoparticle diffusion in gray matter","volume":"25","author":"Chen","year":"2024","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"10.1016\/j.biomaterials.2025.123867_bib27","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jconrel.2023.08.049","article-title":"Poly-\u03b3-glutamic acid nanoparticles as adjuvant and antigen carrier system for cancer vaccination","volume":"362","author":"Mohammadzadeh","year":"2023","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.biomaterials.2025.123867_bib28","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.addr.2011.12.009","article-title":"Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers","volume":"64","author":"Ensign","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"4","key":"10.1016\/j.biomaterials.2025.123867_bib29","doi-asserted-by":"crossref","DOI":"10.1002\/SMMD.20230029","article-title":"Modification and crosslinking strategies for hyaluronic acid\u2010based hydrogel biomaterials","volume":"2","author":"Luo","year":"2023","journal-title":"Smart Med"},{"key":"10.1016\/j.biomaterials.2025.123867_bib30","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abf9180","article-title":"Targeting Alzheimer's disease with multimodal polypeptide-based nanoconjugates","volume":"7","author":"Duro-Castano","year":"2021","journal-title":"Sci. Adv."},{"key":"10.1016\/j.biomaterials.2025.123867_bib31","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1038\/s41598-020-58974-9","article-title":"Effective nephroprotection against acute kidney injury with a star-shaped polyglutamate-curcuminoid conjugate","volume":"10","author":"C\u00f3rdoba-David","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.biomaterials.2025.123867_bib32","doi-asserted-by":"crossref","DOI":"10.1002\/adma.202417348","article-title":"Off\u2010the\u2010shelf multivalent nanoconjugate cancer vaccine rescues host immune response against melanoma","volume":"37","author":"Moura","year":"2025","journal-title":"Adv. Mater."},{"key":"10.1016\/j.biomaterials.2025.123867_bib33","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.3390\/ph17091180","article-title":"Review of intranasal active pharmaceutical ingredient delivery systems","volume":"17","author":"Safarov","year":"2024","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.biomaterials.2025.123867_bib34","doi-asserted-by":"crossref","first-page":"10444","DOI":"10.3390\/cimb46090621","article-title":"Hyaluronic acid in nanopharmaceuticals: an overview","volume":"46","author":"Matalqah","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib35","doi-asserted-by":"crossref","first-page":"854","DOI":"10.3390\/pharmaceutics13060854","article-title":"Thiolated-polymer-based nanoparticles as an avant-garde approach for anticancer therapies\u2014reviewing thiomers from chitosan and hyaluronic acid","volume":"13","author":"Grosso","year":"2021","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.biomaterials.2025.123867_bib36","article-title":"Thiolated polymers: an overview of mucoadhesive properties and their potential in drug delivery via mucosal tissues","volume":"85","author":"Mfoafo","year":"2023","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.addr.2019.04.007","article-title":"Thiolated polymers: bioinspired polymers utilizing one of the Most important bridging structures in nature","volume":"151\u2013152","author":"Leichner","year":"2019","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.biomaterials.2025.123867_bib38","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jconrel.2011.02.022","article-title":"Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson's disease following intranasal administration","volume":"151","author":"Wen","year":"2011","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.biomaterials.2025.123867_bib39","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.ejpb.2011.10.012","article-title":"A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-\u03b225\u201335-treated rats following intranasal administration","volume":"80","author":"Wu","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.biomaterials.2025.123867_bib40","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0002381","article-title":"Odorranalectin is a small peptide lectin with potential for drug delivery and targeting","volume":"3","author":"Li","year":"2008","journal-title":"PLoS One"},{"key":"10.1016\/j.biomaterials.2025.123867_bib41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2147\/IJN.S481917","article-title":"Hyaluronic acid-based hybrid nanoparticles as promising carriers for the intranasal administration of dimethyl fumarate","volume":"20","author":"Serri","year":"2025","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.biomaterials.2025.123867_bib42","article-title":"Efficacy of hyaluronic acid in the treatment of nasal inflammatory diseases: a systematic review and meta-analysis","volume":"15","author":"Liu","year":"2024","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib43","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.ejpb.2015.08.008","article-title":"Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: role of docosahexaenoic acid","volume":"96","author":"Shinde","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.biomaterials.2025.123867_bib44","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2023.1341295","article-title":"Research progress in brain-targeted nasal drug delivery","volume":"15","author":"Huang","year":"2024","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.biomaterials.2025.123867_bib45","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.ijbiomac.2019.11.066","article-title":"Hyaluronic acid: a review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies","volume":"151","author":"Vasvani","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib46","article-title":"Chitosan nanoparticles for nasal drug delivery","volume":"105","author":"Alghareeb","year":"2025","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib47","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.3109\/10717544.2014.975382","article-title":"Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study","volume":"23","author":"Madane","year":"2016","journal-title":"Drug Deliv."},{"key":"10.1016\/j.biomaterials.2025.123867_bib48","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ijdevneu.2019.10.004","article-title":"Docosahexaenoic acid, 22:6n\u20103: its roles in the structure and function of the brain","volume":"79","author":"Mallick","year":"2019","journal-title":"Int. J. Dev. Neurosci."},{"key":"10.1016\/j.biomaterials.2025.123867_bib49","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.3390\/pharmaceutics14071353","article-title":"In vitro anatomical models for nasal drug delivery","volume":"14","author":"Williams","year":"2022","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.biomaterials.2025.123867_bib50","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.3390\/biomedicines11082198","article-title":"Computational, in vitro, and in vivo models for nose-to-brain drug delivery studies","volume":"11","author":"Boyuklieva","year":"2023","journal-title":"Biomedicines"},{"key":"10.1016\/j.biomaterials.2025.123867_bib51","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.addr.2020.09.002","article-title":"In vitro \u2013 in vivo correlation of intranasal drug deposition","volume":"170","author":"Le Guellec","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.biomaterials.2025.123867_bib52","series-title":"Concepts and Models for Drug Permeability Studies","year":"2016"},{"key":"10.1016\/j.biomaterials.2025.123867_bib53","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1002\/bdd.2348","article-title":"In vitro and ex vivo experimental models for evaluation of intranasal systemic drug delivery as well as direct nose\u2010to\u2010brain drug delivery","volume":"44","author":"Haasbroek\u2010Pheiffer","year":"2023","journal-title":"Biopharm. Drug Dispos."},{"key":"10.1016\/j.biomaterials.2025.123867_bib54","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/s41398-021-01511-7","article-title":"Nasal oxytocin for the treatment of psychiatric disorders and pain: achieving meaningful brain concentrations","volume":"11","author":"Yeomans","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"10.1016\/j.biomaterials.2025.123867_bib55","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.drudis.2010.03.011","article-title":"New strategies to improve the intranasal absorption of insulin","volume":"15","author":"Duan","year":"2010","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.biomaterials.2025.123867_bib56","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.3233\/JAD-161256","article-title":"Effects of regular and long-acting insulin on cognition and alzheimer's disease biomarkers: a pilot clinical trial","volume":"57","author":"Craft","year":"2017","journal-title":"J. Alzheim. Dis."},{"key":"10.1016\/j.biomaterials.2025.123867_bib57","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics15051557","article-title":"Challenges in the development and application of organ-on-chips for intranasal drug delivery studies","volume":"15","author":"Usman Khan","year":"2023","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.biomaterials.2025.123867_bib84","doi-asserted-by":"crossref","DOI":"10.1016\/j.addr.2022.114485","article-title":"Lipid nanoparticles strategies to modify pharmacokinetics of central nervous system targeting drugs: crossing or circumventing the blood\u2013brain barrier (BBB) to manage neurological disorders","volume":"189","author":"Correia","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.biomaterials.2025.123867_bib58","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.biomaterials.2018.09.023","article-title":"Tumor microenvironment-targeted poly-L-glutamic acid-based combination conjugate for enhanced triple negative breast cancer treatment","volume":"186","author":"Arroyo-Crespo","year":"2018","journal-title":"Biomaterials"},{"key":"10.1016\/j.biomaterials.2025.123867_bib59","doi-asserted-by":"crossref","DOI":"10.1039\/c3py00347g","article-title":"A controlled and versatile NCA polymerization method for the synthesis of polypeptides","volume":"4","author":"Conejos-S\u00e1nchez","year":"2013","journal-title":"Polym. Chem."},{"key":"10.1016\/j.biomaterials.2025.123867_bib60","article-title":"A targeted polypeptide-based nanoconjugate as a nanotherapeutic for alcohol-induced neuroinflammation","volume":"34","author":"Cuesta","year":"2021","journal-title":"Nanomedicine"},{"key":"10.1016\/j.biomaterials.2025.123867_bib61","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejpb.2014.03.004","article-title":"Intranasal delivery of systemic-acting drugs: small-Molecules and biomacromolecules","volume":"88","author":"Fortuna","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.biomaterials.2025.123867_bib62","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.927812","article-title":"Editorial: intranasal delivery of central nervous system active drugs: opportunities and challenges","volume":"13","author":"Rodrigues","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib63","doi-asserted-by":"crossref","first-page":"7603","DOI":"10.1039\/D0PY01215G","article-title":"Pyridyl disulfide-based thiol\u2013disulfide exchange reaction: shaping the design of redox-responsive polymeric materials","volume":"11","author":"Altinbasak","year":"2020","journal-title":"Polym. Chem."},{"key":"10.1016\/j.biomaterials.2025.123867_bib64","article-title":"Pyridyl disulfide functionalized polymers as nanotherapeutic platforms","volume":"2","author":"Sui","year":"2019","journal-title":"Adv. Ther."},{"key":"10.1016\/j.biomaterials.2025.123867_bib65","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jconrel.2013.11.005","article-title":"A facile approach for dual-responsive prodrug nanogels based on dendritic polyglycerols with minimal leaching","volume":"174","author":"Zhang","year":"2014","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.biomaterials.2025.123867_bib66","doi-asserted-by":"crossref","first-page":"398","DOI":"10.3390\/polym10040398","article-title":"A facile, one-pot, surfactant-free nanoprecipitation method for the preparation of nanogels from polyglycerol\u2013drug conjugates that can be freely assembled for combination therapy applications","volume":"10","author":"Vossen","year":"2018","journal-title":"Polymers (Basel)"},{"key":"10.1016\/j.biomaterials.2025.123867_bib67","doi-asserted-by":"crossref","first-page":"8638","DOI":"10.1039\/D0OB01475C","article-title":"Deprotection of S -acetamidomethyl cysteine with copper( <scp>ii<\/scp> ) and 1,2-aminothiols under aerobic conditions","volume":"18","author":"Kobayashi","year":"2020","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.biomaterials.2025.123867_bib68","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1021\/ol048771l","article-title":"Highly efficient stereoconservative amidation and deamidation of \u03b1-Amino acids","volume":"6","author":"Shendage","year":"2004","journal-title":"Org. Lett."},{"key":"10.1016\/j.biomaterials.2025.123867_bib69","doi-asserted-by":"crossref","DOI":"10.1002\/adhm.202002121","article-title":"Polymer conjugation of docosahexaenoic acid potentiates cardioprotective therapy in preclinical models of myocardial Ischemia\/Reperfusion injury","volume":"10","author":"Tejedor","year":"2021","journal-title":"Adv. Healthcare Mater."},{"key":"10.1016\/j.biomaterials.2025.123867_bib70","doi-asserted-by":"crossref","unstructured":"I. Dolz-P\u00e9rez, M.A. Sallam, E. Masi\u00e1, D. Morell\u00f3-Bolumar, M.D. P\u00e9rez del Caz, P. Graff, D. Abdelmonsif, S. Hedtrich, V.J. Nebot, M.J. Vicent, Polypeptide-corticosteroid conjugates as a topical treatment approach to psoriasis, J. Contr. Release 318 (2020) 210\u2013222. https:\/\/doi.org\/10.1016\/j.jconrel.2019.12.016.","DOI":"10.1016\/j.jconrel.2019.12.016"},{"key":"10.1016\/j.biomaterials.2025.123867_bib71","doi-asserted-by":"crossref","DOI":"10.1177\/2041731417726464","article-title":"Crosslinking method of hyaluronic-based hydrogel for biomedical applications","volume":"8","author":"Khunmanee","year":"2017","journal-title":"J. Tissue Eng."},{"key":"10.1016\/j.biomaterials.2025.123867_bib72","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.carbpol.2011.12.004","article-title":"SEC determination of cross-link efficiency in hyaluronan fillers","volume":"88","author":"Guarise","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"10.1016\/j.biomaterials.2025.123867_bib73","first-page":"291","article-title":"Molar mass - intrinsic viscosity relationship of high-molar-mass hyaluronans: involvement of shear rate","volume":"59","author":"Lath","year":"2005","journal-title":"Chem. Pap."},{"key":"10.1016\/j.biomaterials.2025.123867_bib74","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.carres.2016.07.013","article-title":"Hyaluronic acid auto-crosslinked polymer (ACP): reaction monitoring, process investigation and hyaluronidase stability","volume":"433","author":"Pluda","year":"2016","journal-title":"Carbohydr. Res."},{"key":"10.1016\/j.biomaterials.2025.123867_bib75","series-title":"ICH Guidelines Q3A\u2013Q3D: Impurities in New Drug Substances, Drug Products, Residual Solvents, and Elemental Impurities","year":"2025"},{"key":"10.1016\/j.biomaterials.2025.123867_bib76","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/(SICI)1520-6017(200003)89:3<396::AID-JPS10>3.0.CO;2-F","article-title":"Validation of excised bovine nasal mucosa as in vitro model to study drug transport and metabolic pathways in nasal epithelium","volume":"89","author":"Schmidt","year":"2000","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.biomaterials.2025.123867_bib77","doi-asserted-by":"crossref","DOI":"10.1002\/advs.202102451","article-title":"Thiolated nanoparticles for biomedical applications: mimicking the workhorses of our body","volume":"9","author":"Hock","year":"2022","journal-title":"Adv. Sci."},{"key":"10.1016\/j.biomaterials.2025.123867_bib78","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nchembio.451","article-title":"Coupling of receptor conformation and ligand orientation determine graded activity","volume":"6","author":"Bruning","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.biomaterials.2025.123867_bib79","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.jconrel.2023.07.020","article-title":"Controlled spatial characteristics of ligands on nanoparticles: determinant of cellular functions","volume":"360","author":"Choi","year":"2023","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.biomaterials.2025.123867_bib80","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s40263-022-00930-4","article-title":"Using the intranasal route to administer drugs to treat neurological and psychiatric illnesses: Rationale, successes, and future needs","volume":"36","author":"Lofts","year":"2022","journal-title":"CNS Drugs"},{"key":"10.1016\/j.biomaterials.2025.123867_bib81","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.jconrel.2024.06.056","article-title":"Minimally invasive nasal infusion (MINI) approach for CNS delivery of protein therapeutics: a case study with ovalbumin","volume":"372","author":"Di Francesco","year":"2024","journal-title":"J. Contr. Release"},{"key":"10.1016\/j.biomaterials.2025.123867_bib82","doi-asserted-by":"crossref","DOI":"10.1002\/adfm.201800931","article-title":"Anticancer activity driven by drug linker modification in a polyglutamic acid\u2010based combination\u2010drug conjugate","volume":"28","author":"Arroyo\u2010Crespo","year":"2018","journal-title":"Adv. Funct. Mater."},{"key":"10.1016\/j.biomaterials.2025.123867_bib83","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1039\/D4PM00057A","article-title":"Insight into central nervous system targeted nanostructured lipid carriers via the nose to brain pathway","volume":"1","author":"Das","year":"2024","journal-title":"RSC Pharmaceutics"},{"key":"10.1016\/j.biomaterials.2025.123867_bib85","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40035-025-00481-w","article-title":"Nose-to-brain drug delivery: from bench to bedside","volume":"14","author":"Drath","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"10.1016\/j.biomaterials.2025.123867_bib86","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.3390\/pharmaceutics15102508","article-title":"Polysaccharide-based nanogels to overcome mucus, skin, cornea, and blood-brain barriers: a review","volume":"15","author":"Wang","year":"2023","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.biomaterials.2025.123867_bib87","doi-asserted-by":"crossref","first-page":"775","DOI":"10.3390\/pharmaceutics17060775","article-title":"Intranasal drug delivery technology in the treatment of central nervous system diseases: challenges, advances, and future research directions","volume":"17","author":"Wu","year":"2025","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.biomaterials.2025.123867_bib88","doi-asserted-by":"crossref","first-page":"450","DOI":"10.7150\/thno.21668","article-title":"Breaking the barrier - potent anti-inflammatory activity following efficient topical delivery of etanercept using thermoresponsive nanogels","volume":"8","author":"Giulbudagian","year":"2018","journal-title":"Theranostics"},{"key":"10.1016\/j.biomaterials.2025.123867_bib89","doi-asserted-by":"crossref","DOI":"10.1016\/j.xpro.2022.101419","article-title":"Isolation, cultivation, and application of primary respiratory epithelial cells obtained by nasal brushing, polyp samples, or lung explants","volume":"3","author":"Golec","year":"2022","journal-title":"STAR Protoc."},{"key":"10.1016\/j.biomaterials.2025.123867_bib90","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"}],"container-title":["Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0142961225007872?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0142961225007872?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:31:39Z","timestamp":1777397499000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0142961225007872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":90,"alternative-id":["S0142961225007872"],"URL":"https:\/\/doi.org\/10.1016\/j.biomaterials.2025.123867","relation":{},"ISSN":["0142-9612"],"issn-type":[{"value":"0142-9612","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A rationally designed polypeptide-based hybrid platform for targeted intranasal brain drug delivery","name":"articletitle","label":"Article Title"},{"value":"Biomaterials","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biomaterials.2025.123867","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"123867"}}