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Microneedle (MN) technology has emerged as a minimally invasive strategy for transdermal delivery and as a platform for functional polymeric microdevices. In this study, polycaprolactone (PCL) microneedles coated with hydrophilic polymers were evaluated as a model platform for antigen delivery. Ex vivo assays using porcine ear skin were explored as a preliminary approach to assess antigen transport from polymer-coated PCL microneedles. However, antigen-specific quantification in the receptor compartment was limited by the lack of specificity of absorbance-based measurements in this biological matrix. Scanning electron microscopy (SEM) showed that PVA coating partially altered microneedle tip morphology, whereas optical coherence tomography (OCT) and optical microscopy confirmed that PVA20%-PCL-MNs maintained the ability to insert into porcine skin and generate visible insertion sites. Mechanical compression testing further showed that polymer-coated PCL-MNs maintained resistance to axial deformation under the tested conditions. PVA20%-PCL-MNs were also non-toxic and maintained high HEK293T cell viability after 24 h. Based on their preserved insertion capacity, mechanical robustness, ability to support DNP-KLH permeation, and preliminary cytocompatibility, PVA20%-PCL-MNs were evaluated in BALB\/c mice using a two-dose prime-boost regimen. Although intraperitoneal immunization induced higher IgG levels, transdermal immunization with PVA20%-PCL-MNs promoted booster-dependent antigen-specific IgG responses. IgG2a\/IgG1 ratio analysis indicated a predominantly IgG1-biased humoral profile, and splenocytes from mice immunized with PVA20%-PCL-MNs produced detectable levels of IFN-\u03b3 and IL-10 after in vitro stimulation. Together, these findings support PVA-coated PCL microneedles as a proof-of-concept polymeric microdevice platform for minimally invasive antigen delivery and immunogenicity assessment.<\/jats:p>","DOI":"10.3390\/polym18192327","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:07:54Z","timestamp":1790240874000},"page":"2327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyvinyl Alcohol-Coated Polycaprolactone Microneedles as Polymeric Microdevices for Transdermal Antigen Delivery and Immune Activation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1171-8312","authenticated-orcid":false,"given":"Aline F.","family":"Teixeira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Desenvolvimento de Vacinas, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro T.","family":"Kochi","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias Naturais e Humanas, Universidade Federal do ABC, Santo Andr\u00e9 09210-580, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3301-6213","authenticated-orcid":false,"given":"Ana Carola","family":"De La Via Reis","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias Naturais e Humanas, Universidade Federal do ABC, Santo Andr\u00e9 09210-580, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Rojas","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias Naturais e Humanas, Universidade Federal do ABC, Santo Andr\u00e9 09210-580, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9289-4229","authenticated-orcid":false,"given":"Daniele Ribeiro de","family":"Araujo","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Universidade Federal de S\u00e3o Paulo, S\u00e3o Paulo 04021-001, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8394-2751","authenticated-orcid":false,"given":"Wendel A.","family":"Alves","sequence":"additional","affiliation":[{"name":"Centro de Ci\u00eancias Naturais e Humanas, Universidade Federal do ABC, Santo Andr\u00e9 09210-580, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4851-0870","authenticated-orcid":false,"given":"Ana Lucia T. 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Macromol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"124734","DOI":"10.1016\/j.ijpharm.2024.124734","article-title":"Recent trends on polycaprolactone as sustainable polymer-based drug delivery system in the treatment of cancer: Biomedical applications and nanomedicine","volume":"666","author":"Raza","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.contraception.2006.02.013","article-title":"A biodegradable levonorgestrel-releasing implant made of PCL\/F68 compound as tested in rats and dogs","volume":"74","author":"Ma","year":"2006","journal-title":"Contraception"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1021\/acsabm.2c00174","article-title":"Current Applications of Polycaprolactone as a Scaffold Material for Heart Regeneration","volume":"5","author":"Schmitt","year":"2022","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ntrivala, M.A.G., Balla, E.D., Klonos, P.A., Kyritsis, A., and Bikiaris, D.N. (2025). Synthesis and Characterization of Novel Non-Isocyanate Polyurethanes Derived from Adipic Acid: A Comprehensive Study. Polymers, 17.","DOI":"10.3390\/polym17060728"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1039\/C5TB02240A","article-title":"Polycaprolactone fibers with self-assembled peptide micro\/nanotubes: A practical route towards enhanced mechanical strength and drug delivery applications","volume":"4","author":"Liberato","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1021\/acsabm.5c01937","article-title":"Polypyrrole-Coated Microneedle Platform for Offline Electrochemical Detection of Interferon-Alpha in Interstitial Fluid","volume":"9","author":"Reis","year":"2026","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1021\/acsbiomaterials.1c00913","article-title":"Silk Fibroin\/Poly(vinyl Alcohol) Microneedles as Carriers for the Delivery of Singlet Oxygen Photosensitizers","volume":"8","author":"Oliveira","year":"2022","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"341","DOI":"10.4269\/ajtmh.2003.68.341","article-title":"Fear of injections in young adults: Prevalence and associations","volume":"68","author":"Nir","year":"2003","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e04342","DOI":"10.1002\/adhm.202504342","article-title":"Microneedles Based Thermally Stable Ad-5 Viral Vector for Vaccine Delivery","volume":"15","author":"Singh","year":"2026","journal-title":"Adv. Healthc. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.addr.2012.04.005","article-title":"Microneedles for drug and vaccine delivery","volume":"64","author":"Kim","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1021\/acs.molpharmaceut.7b00730","article-title":"Adjuvant Activity of Poly-\u03b5-caprolactone\/Chitosan Nanoparticles Characterized by Mast Cell Activation and IFN-\u03b3 and IL-17 Production","volume":"15","author":"Jesus","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1086\/649228","article-title":"Enhanced memory responses to seasonal H1N1 influenza vaccination of the skin with the use of vaccine-coated microneedles","volume":"201","author":"Kim","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ejpb.2012.03.010","article-title":"Increased immunogenicity of avian influenza DNA vaccine delivered to the skin using a microneedle patch","volume":"81","author":"Kim","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/19\/2327\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:20:40Z","timestamp":1790396440000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/18\/19\/2327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":25,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["polym18192327"],"URL":"https:\/\/doi.org\/10.3390\/polym18192327","relation":{},"ISSN":["2073-4360"],"issn-type":[{"value":"2073-4360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}