{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:07:01Z","timestamp":1789024021968,"version":"build-2803163510"},"reference-count":203,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Chemical Record"],"abstract":"<jats:p>Transdermal drug delivery (TDD) is reemerging as a clinically attractive route for noninvasive therapy, driven by the growing demand for alternatives to repeated injection and by the rapid development of materials capable of regulating transport across the skin. By avoiding gastrointestinal degradation and hepatic first\u2010pass metabolism, TDD can provide prolonged drug exposure, reduce peak\u2010to\u2010trough fluctuations in plasma concentration, and improve adherence in long\u2010term treatment. Its broader implementation, however, is still constrained by the exceptional barrier function of the stratum corneum, which severely limits the passive transport of hydrophilic molecules, charged species, and macromolecular therapeutics. In this review, we critically discuss the structural basis of the skin barrier and summarize the evolution of TDD strategies from conventional chemical permeation enhancement and device\u2010assisted physical disruption to nanocarrier\u2010mediated, biomimetic, and intelligent bio\u2010delivery systems. Particular emphasis is placed on the mechanistic logic that connects carrier composition, interfacial interactions, skin microenvironment remodeling, and therapeutic performance. Representative examples are analyzed to highlight both opportunities and translational bottlenecks. Finally, we outline future directions in multimodal delivery, pathology\u2010adapted design, standardized evaluation, and scalable manufacturing, which will be essential for transforming TDD from a permeability enhancement technology into a precision\u2010regulated therapeutic platform.<\/jats:p>","DOI":"10.1002\/tcr.70249","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:37:54Z","timestamp":1789022274000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Barrier Disruption to Precision Skin Interface Engineering: Next\u2010Generation Transdermal Drug Delivery"],"prefix":"10.1002","author":[{"given":"Cong\u2010Zheng","family":"Zhou","sequence":"first","affiliation":[{"name":"Lab of Functional and Biomedical Nanomaterials College of Materials Science and Engineering Qingdao University of Science and Technology (QUST)  Qingdao P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin\u2010Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Lab of Functional and Biomedical Nanomaterials College of Materials Science and Engineering Qingdao University of Science and Technology (QUST)  Qingdao P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou\u2010Shan","family":"Yu","sequence":"additional","affiliation":[{"name":"Lab of Functional and Biomedical Nanomaterials College of Materials Science and Engineering Qingdao University of Science and Technology (QUST)  Qingdao P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5006-5257","authenticated-orcid":false,"given":"Sheng\u2010Lin","family":"Qiao","sequence":"additional","affiliation":[{"name":"Lab of Functional and Biomedical Nanomaterials College of Materials Science and Engineering Qingdao University of Science and Technology (QUST)  Qingdao P. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"103002","DOI":"10.1016\/j.mtbio.2026.103002","article-title":"Transdermal Needle\u2010Free Drug Delivery Approaches and Activation Mechanism","volume":"38","author":"Sasikala A.","year":"2026","journal-title":"Materials Today Bio"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"2104092","DOI":"10.1002\/adfm.202104092","article-title":"Self\u2010Powered Controllable Transdermal Drug Delivery System","volume":"31","author":"Yang Y.","year":"2021","journal-title":"Advanced Functional Materials"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"2306944","DOI":"10.1002\/smll.202306944","article-title":"Smart Physical\u2010Based Transdermal Drug Delivery System: Towards Intelligence and Controlled Release","volume":"20","author":"Zhang H.","year":"2024","journal-title":"Small"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"114753","DOI":"10.1016\/j.addr.2023.114753","article-title":"Transdermal Drug Delivery via Microneedles to Mediate Wound Microenvironment","volume":"195","author":"Mo R.","year":"2023","journal-title":"Advanced Drug Delivery Reviews"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","first-page":"100375","DOI":"10.1016\/j.celbio.2026.100375","article-title":"Tissue\u2010Fluid\u2010Driven Symbiotic Electronic Textile Accelerates and Guides Tissue Self\u2010Healing","volume":"2","author":"Wang E.","year":"2026","journal-title":"Cell Biomaterials"},{"key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41528-026-00574-0","article-title":"Bioabsorbable Si\u2010Mg Galvanic Cells in Flexible Scaffolds for Symbiotic Electrical Stimulation to Promote Nerve Regeneration","volume":"10","author":"Wang E.","year":"2026","journal-title":"NPJ Flexible Electronics"},{"key":"e_1_2_12_8_1","first-page":"869","article-title":"Author Correction: Acoustic Metamaterials\u2010Driven Transdermal Drug Delivery for Rapid and on\u2010Demand Management of Acute Disease","volume":"17","author":"Xu J.","year":"2026","journal-title":"Nature Communications"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"4062","DOI":"10.1038\/s41467-024-48226-z","article-title":"Three Stepwise pH Progressions in Stratum Corneum for Homeostatic Maintenance of the Skin","volume":"15","author":"Fukuda K.","year":"2024","journal-title":"Nature Communications"},{"key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"1901103","DOI":"10.1002\/adma.201901103","article-title":"Design Principles of Ionic Liquids for Transdermal Drug Delivery","volume":"31","author":"Tanner E. 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