{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:33:31Z","timestamp":1792089211371,"version":"4.4.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012331","name":"Agentschap Innoveren en Ondernemen","doi-asserted-by":"publisher","award":["HBC.2019.2931"],"award-info":[{"award-number":["HBC.2019.2931"]}],"id":[{"id":"10.13039\/100012331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mucosal vaccination generates protective immune responses directly at the primary site of STI infection. However, the delivery of nanoparticles is hindered by the mucus barrier at these mucosal surfaces. Due to this interference, research on mucosal administration of self-amplifying (sa)-mRNA encapsulated in lipid nanoparticles (LNP) is currently limited and inconsistent. Some progress has been reported for nasal mRNA vaccination. However, for STIs, protective immune responses are required at the urogenital tract, which is achieved through intravaginal or intranasal administration. Therefore, in this research, we aimed to determine whether an sa-mRNA-LNP reporter vaccine could be effectively administered mucosally, evaluating its potential as a novel platform for STI vaccination. The sa-mRNA luciferase construct was encapsulated in two LNP formulations. In vitro studies demonstrated that these formulations maintained their potency after being sprayed with different sprayers and exposed to different mucus solutions, except for a human cervicovaginal simulant. Next, pigs received 15\u00a0\u00b5g of the sa-mRNA intravaginally and intranasally through a mucosal spray or injection. The mucosal spray resulted in expression and uptake only at the vaginal mucosa, whereas injection of the formulations resulted in expression at both mucosal sites. However, expression after spraying in the vaginal mucosa disappeared by day 4 post-administration. No differences were observed between both LNP formulations. These findings demonstrate that sa-mRNA can be used for mucosal administration, and expression can be achieved in a more relevant animal model. However, additional research is needed to develop more suitable particles for these complex environments.<\/jats:p>","DOI":"10.1007\/s13346-025-01877-x","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T09:51:55Z","timestamp":1749635515000},"page":"330-346","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mucosal administration of lipid nanoparticles containing self-amplifying mRNA induces local uptake and expression in a pig model as a potential vaccination platform against STIs"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8732-7783","authenticated-orcid":false,"given":"Ibe","family":"Van de Casteele","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magalie","family":"Plovyt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Stuchl\u00edkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"Lanssens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Verschueren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quenten","family":"Denon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Van der Meeren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"McCafferty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arlieke","family":"Gitsels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Cornillie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niek N.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aster","family":"Vandierendonck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien C. K.","family":"Poelaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisy","family":"Vanrompay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"1877_CR1","unstructured":"WHO. Sexually transmitted infections (STIs) https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/sexually-transmitted-infections-(stis) 2024 (accessed October 8, 2023)"},{"key":"1877_CR2","doi-asserted-by":"publisher","unstructured":"Nerlander L, Champezou L, Dias JG, Aspelund G, Berlot L, Constantinou E, et al. Sharp increase in gonorrhoea notifications among young people, EU\/EEA, July 2022 to June 2023. Eurosurveillance 2024;29https:\/\/doi.org\/10.2807\/1560-7917.ES.2024.29.10.2400113","DOI":"10.2807\/1560-7917.ES.2024.29.10.2400113"},{"key":"1877_CR3","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1111\/CED.15223","volume":"47","author":"F Fatima","year":"2022","unstructured":"Fatima F, Kumar S, Das A. Vaccines against sexually transmitted infections: an update. Clin Exp Dermatol. 2022;47:1454\u201363. https:\/\/doi.org\/10.1111\/CED.15223.","journal-title":"Clin Exp Dermatol"},{"key":"1877_CR4","first-page":"9","volume":"45","author":"AR Raccagni","year":"2022","unstructured":"Raccagni AR, Alberton F, Castagna A, Nozza S. Vaccines against emerging sexually transmitted infections: current Preventive Tools and Future Perspectives. New Microbiol. 2022;45:9\u201327.","journal-title":"New Microbiol"},{"key":"1877_CR5","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1038\/S41564-022-01177-X","volume":"7","author":"OT Van Gerwen","year":"2022","unstructured":"Van Gerwen OT, Muzny CA, Marrazzo JM. Sexually transmitted infections and female reproductive health. Nat Microbiol. 2022;7:1116\u201326. https:\/\/doi.org\/10.1038\/S41564-022-01177-X.","journal-title":"Nat Microbiol"},{"issue":"4","key":"1877_CR6","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.1038\/nm1213","volume":"11","author":"J Holmgren","year":"2005","unstructured":"Holmgren J, Czerkinsky C. Mucosal immunity and vaccines. Nat Med. 2005;11(4):S45-53. https:\/\/doi.org\/10.1038\/nm1213.","journal-title":"Nat Med"},{"key":"1877_CR7","doi-asserted-by":"publisher","first-page":"235","DOI":"10.7774\/CEVR.2022.11.3.235","volume":"11","author":"R Anggraeni","year":"2022","unstructured":"Anggraeni R, Ana ID, Wihadmadyatami H. Development of mucosal vaccine delivery: an overview on the mucosal vaccines and their adjuvants. Clin Exp Vaccine Res. 2022;11:235. https:\/\/doi.org\/10.7774\/CEVR.2022.11.3.235.","journal-title":"Clin Exp Vaccine Res"},{"key":"1877_CR8","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1242\/JCS.193482","volume":"130","author":"MM France","year":"2017","unstructured":"France MM, Turner JR. The mucosal barrier at a glance. J Cell Sci. 2017;130:307. https:\/\/doi.org\/10.1242\/JCS.193482.","journal-title":"J Cell Sci"},{"key":"1877_CR9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/J.JACI.2022.05.002","volume":"150","author":"JR Baker","year":"2022","unstructured":"Baker JR, Farazuddin M, Wong PT, O\u2019Konek JJ. The unfulfilled potential of mucosal immunization. J Allergy Clin Immunol. 2022;150:1. https:\/\/doi.org\/10.1016\/J.JACI.2022.05.002.","journal-title":"J Allergy Clin Immunol"},{"issue":"3","key":"1877_CR10","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/s41385-021-00471-x","volume":"15","author":"BR Traxinger","year":"2021","unstructured":"Traxinger BR, Richert-Spuhler LE, Lund JM. Mucosal tissue regulatory T cells are integral in balancing immunity and tolerance at portals of antigen entry. Mucosal Immunol. 2021;15(3):398\u2013407. https:\/\/doi.org\/10.1038\/s41385-021-00471-x.","journal-title":"Mucosal Immunol"},{"key":"1877_CR11","doi-asserted-by":"publisher","unstructured":"Verma SK, Mahajan P, Singh NK, Gupta A, Aggarwal R, Rappuoli R, et al. New-age vaccine adjuvants, their development, and future perspective. Front Immunol 2023;14. https:\/\/doi.org\/10.3389\/FIMMU.2023.1043109","DOI":"10.3389\/FIMMU.2023.1043109"},{"key":"1877_CR12","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1016\/J.YMTHE.2022.01.001","volume":"30","author":"G Maruggi","year":"2022","unstructured":"Maruggi G, Mallett CP, Westerbeck JW, Chen T, Lofano G, Friedrich K, et al. A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models. Mol Ther. 2022;30:1897. https:\/\/doi.org\/10.1016\/J.YMTHE.2022.01.001.","journal-title":"Mol Ther"},{"key":"1877_CR13","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1016\/J.IMMUNI.2022.10.014","volume":"55","author":"R Verbeke","year":"2022","unstructured":"Verbeke R, Hogan MJ, Lor\u00e9 K, Pardi N. Innate immune mechanisms of mRNA vaccines. Immunity. 2022;55:1993\u20132005. https:\/\/doi.org\/10.1016\/J.IMMUNI.2022.10.014.","journal-title":"Immunity"},{"issue":"1","key":"1877_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41541-022-00485-x","volume":"7","author":"SA Hameed","year":"2022","unstructured":"Hameed SA, Paul S, Dellosa GKY, Jaraquemada D, Bello MB. Towards the future exploration of mucosal mRNA vaccines against emerging viral diseases; lessons from existing next-generation mucosal vaccine strategies. Npj Vaccines. 2022;7(1):1\u201320. https:\/\/doi.org\/10.1038\/s41541-022-00485-x.","journal-title":"Npj Vaccines"},{"key":"1877_CR15","doi-asserted-by":"publisher","unstructured":"Jennewein MF, Schultz MD, Beaver S, Battisti P, Bakken J, Hanson D, et al. Intranasal self-amplifying RNA SARS-CoV-2 vaccine produces protective respiratory and systemic immunity and prevents viral transmission. BioRxiv 2023:2022.11.10.515993. https:\/\/doi.org\/10.1101\/2022.11.10.515993","DOI":"10.1101\/2022.11.10.515993"},{"key":"1877_CR16","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/J.JCONREL.2021.12.008","volume":"342","author":"G Anderluzzi","year":"2022","unstructured":"Anderluzzi G, Lou G, Woods S, Schmidt ST, Gallorini S, Brazzoli M, et al. The role of nanoparticle format and route of administration on self-amplifying mRNA vaccine potency. J Control Release. 2022;342:388\u201399. https:\/\/doi.org\/10.1016\/J.JCONREL.2021.12.008.","journal-title":"J Control Release"},{"key":"1877_CR17","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/J.ADDR.2017.11.001","volume":"124","author":"JY Lock","year":"2018","unstructured":"Lock JY, Carlson TL, Carrier RL. Mucus models to evaluate the diffusion of drugs and particles. Adv Drug Deliv Rev. 2018;124:34. https:\/\/doi.org\/10.1016\/J.ADDR.2017.11.001.","journal-title":"Adv Drug Deliv Rev"},{"key":"1877_CR18","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1021\/ACSBIOMATERIALS.2C00047\/ASSET\/IMAGES\/LARGE\/AB2C00047_0009.JPEG","volume":"8","author":"J Watchorn","year":"2022","unstructured":"Watchorn J, Clasky AJ, Prakash G, Johnston IAE, Chen PZ, Gu FX. Untangling mucosal drug delivery: Engineering, designing, and testing nanoparticles to overcome the mucus barrier. ACS Biomater Sci Eng. 2022;8:1396\u2013426. https:\/\/doi.org\/10.1021\/ACSBIOMATERIALS.2C00047\/ASSET\/IMAGES\/LARGE\/AB2C00047_0009.JPEG.","journal-title":"ACS Biomater Sci Eng"},{"key":"1877_CR19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1208\/S12249-022-02330-9","volume":"23","author":"L Cai","year":"2022","unstructured":"Cai L, Xu H, Cui Z. Factors limiting the translatability of rodent model-based intranasal vaccine research to humans. AAPS PharmSciTech. 2022;23:3. https:\/\/doi.org\/10.1208\/S12249-022-02330-9.","journal-title":"AAPS PharmSciTech"},{"key":"1877_CR20","doi-asserted-by":"publisher","first-page":"7300","DOI":"10.1021\/ACS.NANOLETT.5B02497\/SUPPL_FILE\/NL5B02497_SI_001.PDF","volume":"15","author":"KJ Kauffman","year":"2015","unstructured":"Kauffman KJ, Dorkin JR, Yang JH, Heartlein MW, Derosa F, Mir FF, et al. Optimization of lipid nanoparticle formulations for mRNA delivery in vivo with fractional factorial and definitive screening designs. Nano Lett. 2015;15:7300\u20136. https:\/\/doi.org\/10.1021\/ACS.NANOLETT.5B02497\/SUPPL_FILE\/NL5B02497_SI_001.PDF.","journal-title":"Nano Lett"},{"key":"1877_CR21","doi-asserted-by":"publisher","first-page":"7597","DOI":"10.1128\/JVI.79.12.7597-7608.2005\/ASSET\/6C80F719-8572-4AF2-B333-EA64C41CF2F9\/ASSETS\/GRAPHIC\/ZJV0120563460008.JPEG","volume":"79","author":"O Petrakova","year":"2005","unstructured":"Petrakova O, Volkova E, Gorchakov R, Paessler S, Kinney RM, Frolov I. Noncytopathic replication of venezuelan equine encephalitis virus and eastern equine encephalitis virus replicons in mammalian cells. J Virol. 2005;79:7597\u2013608. https:\/\/doi.org\/10.1128\/JVI.79.12.7597-7608.2005\/ASSET\/6C80F719-8572-4AF2-B333-EA64C41CF2F9\/ASSETS\/GRAPHIC\/ZJV0120563460008.JPEG.","journal-title":"J Virol"},{"key":"1877_CR22","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1126\/SCIENCE.1248465","volume":"343","author":"JL Hyde","year":"2014","unstructured":"Hyde JL, Gardner CL, Kimura T, White JP, Liu G, Trobaugh DW, et al. A viral RNA structural element alters host recognition of non-self RNA. Science. 2014;343:783. https:\/\/doi.org\/10.1126\/SCIENCE.1248465.","journal-title":"Science"},{"key":"1877_CR23","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/J.OMTN.2019.02.018","volume":"15","author":"M Baiersd\u00f6rfer","year":"2019","unstructured":"Baiersd\u00f6rfer M, Boros G, Muramatsu H, Mahiny A, Vlatkovic I, Sahin U, et al. A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol Ther Nucleic Acids. 2019;15:26. https:\/\/doi.org\/10.1016\/J.OMTN.2019.02.018.","journal-title":"Mol Ther Nucleic Acids"},{"key":"1877_CR24","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1002\/ELPS.201100335","volume":"33","author":"PS Aranda","year":"2012","unstructured":"Aranda PS, Lajoie DM, Jorcyk CL. Bleach gel: a simple agarose gel for analyzing RNA quality. Electrophoresis. 2012;33:366\u20139. https:\/\/doi.org\/10.1002\/ELPS.201100335.","journal-title":"Electrophoresis"},{"key":"1877_CR25","doi-asserted-by":"publisher","first-page":"3347","DOI":"10.1021\/MP300408M\/SUPPL_FILE\/MP300408M_SI_001.PDF","volume":"9","author":"J Das Neves","year":"2012","unstructured":"Das Neves J, Rocha CMR, Gon\u00e7alves MP, Carrier RL, Amiji M, Bahia MF, et al. Interactions of microbicide nanoparticles with a simulated vaginal fluid. Mol Pharm. 2012;9:3347\u201356. https:\/\/doi.org\/10.1021\/MP300408M\/SUPPL_FILE\/MP300408M_SI_001.PDF.","journal-title":"Mol Pharm"},{"key":"1877_CR26","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/J.JAEROSCI.2010.11.002","volume":"42","author":"JD Schroeter","year":"2011","unstructured":"Schroeter JD, Garcia GJM, Kimbell JS. Effects of surface smoothness on inertial particle deposition in human nasal models. J Aerosol Sci. 2011;42:52\u201363. https:\/\/doi.org\/10.1016\/J.JAEROSCI.2010.11.002.","journal-title":"J Aerosol Sci"},{"issue":"1","key":"1877_CR27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-023-35872-4","volume":"13","author":"CJM van Rijn","year":"2023","unstructured":"van Rijn CJM, Vlaming KE, Bem RA, Dekker RJ, Poortinga A, Breit T, et al. Low energy nebulization preserves integrity of SARS-CoV-2 mRNA vaccines for respiratory delivery. Sci Rep. 2023;13(1):1\u20139. https:\/\/doi.org\/10.1038\/s41598-023-35872-4.","journal-title":"Sci Rep"},{"key":"1877_CR28","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/J.MEEGID.2017.11.022","volume":"66","author":"T K\u00e4ser","year":"2018","unstructured":"K\u00e4ser T, Renois F, Wilson HL, Cnudde T, Gerdts V, Dillon JAR, et al. Contribution of the swine model in the study of human sexually transmitted infections. Infect Genet Evol. 2018;66:346\u201360. https:\/\/doi.org\/10.1016\/J.MEEGID.2017.11.022.","journal-title":"Infect Genet Evol"},{"key":"1877_CR29","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/S11095-015-1796-X\/FIGURES\/6","volume":"33","author":"K Remaut","year":"2016","unstructured":"Remaut K, De Clercq E, Andries O, Rombouts K, Van Gils M, Cicchelero L, et al. Aerosolized non-viral nucleic acid delivery in the vaginal tract of pigs. Pharm Res. 2016;33:384\u201394. https:\/\/doi.org\/10.1007\/S11095-015-1796-X\/FIGURES\/6.","journal-title":"Pharm Res"},{"issue":"1","key":"1877_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-79855-1","volume":"11","author":"RM Legere","year":"2021","unstructured":"Legere RM, Cohen ND, Poveda C, Bray JM, Barhoumi R, Szule JA, et al. Safe and effective aerosolization of in vitro transcribed mRNA to the respiratory tract epithelium of horses without a transfection agent. Sci Rep. 2021;11(1):1\u201312. https:\/\/doi.org\/10.1038\/s41598-020-79855-1.","journal-title":"Sci Rep"},{"key":"1877_CR31","doi-asserted-by":"publisher","first-page":"Doc07","DOI":"10.3205\/CTO000071","volume":"9","author":"AG Beule","year":"2010","unstructured":"Beule AG. Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses. GMS Curr Top Otorhinolaryngol Head Neck Surg. 2010;9:Doc07. https:\/\/doi.org\/10.3205\/CTO000071.","journal-title":"GMS Curr Top Otorhinolaryngol Head Neck Surg"},{"key":"1877_CR32","doi-asserted-by":"publisher","first-page":"e76176","DOI":"10.1371\/JOURNAL.PONE.0076176","volume":"8","author":"KM Fahrbach","year":"2013","unstructured":"Fahrbach KM, Malykhina O, Stieh DJ, Hope TJ. Differential binding of IgG and IgA to mucus of the female reproductive tract. PLoS ONE. 2013;8:e76176. https:\/\/doi.org\/10.1371\/JOURNAL.PONE.0076176.","journal-title":"PLoS ONE"},{"key":"1877_CR33","doi-asserted-by":"publisher","first-page":"114266","DOI":"10.1016\/J.EJPB.2024.114266","volume":"198","author":"M Ongun","year":"2024","unstructured":"Ongun M, Lokras AG, Baghel S, Shi Z, Schmidt ST, Franzyk H, et al. Lipid nanoparticles for local delivery of mRNA to the respiratory tract: Effect of PEG-lipid content and administration route. Eur J Pharm Biopharm. 2024;198:114266. https:\/\/doi.org\/10.1016\/J.EJPB.2024.114266.","journal-title":"Eur J Pharm Biopharm"},{"key":"1877_CR34","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1111\/AJI.12230","volume":"71","author":"DJ Anderson","year":"2014","unstructured":"Anderson DJ, Marathe J, Pudney J. The structure of the human vaginal stratum corneum and its role in immune defense. Am J Reprod Immunol. 2014;71:618. https:\/\/doi.org\/10.1111\/AJI.12230.","journal-title":"Am J Reprod Immunol"},{"key":"1877_CR35","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/J.TIBTECH.2011.06.010","volume":"29","author":"CE Badr","year":"2011","unstructured":"Badr CE, Tannous BA. Bioluminescence imaging: progress and applications. Trends Biotechnol. 2011;29:624. https:\/\/doi.org\/10.1016\/J.TIBTECH.2011.06.010.","journal-title":"Trends Biotechnol"},{"key":"1877_CR36","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1021\/ACS.MOLPHARMACEUT.7B00722\/ASSET\/IMAGES\/LARGE\/MP-2017-00722Q_0005.JPEG","volume":"15","author":"B Leyman","year":"2018","unstructured":"Leyman B, Huysmans H, Mc Cafferty S, Combes F, Cox E, Devriendt B, et al. Comparison of the expression kinetics and immunostimulatory activity of replicating mRNA, nonreplicating mRNA, and pDNA after intradermal electroporation in pigs. Mol Pharm. 2018;15:377\u201384. https:\/\/doi.org\/10.1021\/ACS.MOLPHARMACEUT.7B00722\/ASSET\/IMAGES\/LARGE\/MP-2017-00722Q_0005.JPEG.","journal-title":"Mol Pharm"},{"key":"1877_CR37","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1016\/J.YMTHE.2020.01.002","volume":"28","author":"KE Lindsay","year":"2020","unstructured":"Lindsay KE, Vanover D, Thoresen M, King H, Xiao P, Badial P, et al. Aerosol delivery of synthetic mRNA to vaginal mucosa leads to durable expression of broadly neutralizing antibodies against HIV. Mol Ther. 2020;28:805. https:\/\/doi.org\/10.1016\/J.YMTHE.2020.01.002.","journal-title":"Mol Ther"},{"key":"1877_CR38","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1095\/BIOLREPROD.110.090423","volume":"85","author":"CD Blaskewicz","year":"2011","unstructured":"Blaskewicz CD, Pudney J, Anderson DJ. Structure and function of intercellular junctions in human cervical and vaginal mucosal epithelia. Biol Reprod. 2011;85:97\u2013104. https:\/\/doi.org\/10.1095\/BIOLREPROD.110.090423.","journal-title":"Biol Reprod"},{"key":"1877_CR39","doi-asserted-by":"publisher","unstructured":"Miller EA, Beasley DAE, Dunn RR, Archie EA. Lactobacilli dominance and vaginal pH: Why is the human vaginal microbiome unique? Front Microbiol 2016;7. https:\/\/doi.org\/10.3389\/FMICB.2016.01936\/FULL","DOI":"10.3389\/FMICB.2016.01936\/FULL"},{"key":"1877_CR40","doi-asserted-by":"publisher","unstructured":"Koitabashi K, Nagumo H, Nakao M, Machida T, Yoshida K, Sakai-Kato K. Acidic pH-induced changes in lipid nanoparticle membrane packing. Biochimica et Biophysica Acta (BBA) Biomembranes 2021;1863:183627. https:\/\/doi.org\/10.1016\/J.BBAMEM.2021.183627","DOI":"10.1016\/J.BBAMEM.2021.183627"},{"key":"1877_CR41","doi-asserted-by":"publisher","first-page":"102398","DOI":"10.1016\/J.COI.2023.102398","volume":"85","author":"JW Crothers","year":"2023","unstructured":"Crothers JW, Norton EB. Recent advances in enterotoxin vaccine adjuvants. Curr Opin Immunol. 2023;85:102398. https:\/\/doi.org\/10.1016\/J.COI.2023.102398.","journal-title":"Curr Opin Immunol"},{"key":"1877_CR42","doi-asserted-by":"publisher","first-page":"22720","DOI":"10.1039\/C8NR07755J","volume":"10","author":"R M\u00fcnter","year":"2018","unstructured":"M\u00fcnter R, Kristensen K, Pedersb\u00e6k D, Larsen JB, Simonsen JB, Andresen TL. Dissociation of fluorescently labeled lipids from liposomes in biological environments challenges the interpretation of uptake studies. Nanoscale. 2018;10:22720\u20134. https:\/\/doi.org\/10.1039\/C8NR07755J.","journal-title":"Nanoscale"},{"key":"1877_CR43","doi-asserted-by":"publisher","first-page":"E6639","DOI":"10.1073\/PNAS.1606050113\/SUPPL_FILE\/PNAS.201606050SI.PDF","volume":"113","author":"HH Tam","year":"2016","unstructured":"Tam HH, Melo MB, Kang M, Pelet JM, Ruda VM, Foley MH, et al. Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination. Proc Natl Acad Sci U S A. 2016;113:E6639\u201348. https:\/\/doi.org\/10.1073\/PNAS.1606050113\/SUPPL_FILE\/PNAS.201606050SI.PDF.","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["Drug Delivery and Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-025-01877-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13346-025-01877-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-025-01877-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T21:50:00Z","timestamp":1765144200000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13346-025-01877-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["1877"],"URL":"https:\/\/doi.org\/10.1007\/s13346-025-01877-x","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-5682423\/v1","asserted-by":"object"}]},"ISSN":["2190-393X","2190-3948"],"issn-type":[{"value":"2190-393X","type":"print"},{"value":"2190-3948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]},"assertion":[{"value":"7 May 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 June 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The Ethical Committee of the Faculty of Veterinary Sciences of Ghent University approved the in vivo trial (EC2021-022).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Ziphius NV received funding by VLAIO for this project (project: HBC.2019.2931). Magalie Plovyt, Magdalena Stuchl\u00edkov\u00e1, Michiel Lanssens, Ben Verschueren, Aster Vandierendonck and Katrien C.K. Poelaert are current employees of Ziphius NV and may own Ziphius shares\/warrants. Sean McCafferty is a past employee of Ziphius NV and may own Ziphius shares\/warrants. Ibe Van de Casteele is a current employee of Ziphius NV but was employed by Ghent University during the experimental work. During his employment at Ghent University, Ibe Van de Casteele was paid by Ziphius NV. Niek N. Sanders and Daisy Vanrompay were compensated by Ziphius NV for their input during the project. The authors declare no other competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}