{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T13:10:03Z","timestamp":1793797803775,"version":"4.6.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Drug Deliv. and Transl. Res."],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The discovery of proteins that neutralise vascular endothelial growth factors, such as pegaptanib, ranibizumab and aflibercept, can inhibit the process of angiogenesis, thereby restoring eyesight in individuals with retinal vascular disorders. However, due to the posterior location and chronic nature of retinal diseases, a safe and effective intraocular protein delivery system is currently lacking. Thus, dissolving bilayer microneedles (MNs) with the potential to deliver proteins to the back of the eye in an efficient and minimally invasive manner were developed in this study. A model protein, ovalbumin (OVA), was incorporated into MNs fabricated from different polymers, including hyaluronic acid (HA), polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Optimised PVA\/PVP MNs were demonstrated to be robust enough to pierce porcine sclera with\u2009&gt;\u200975% of the needle length penetrating the sclera and dissolving within 150\u00a0s. SDS-PAGE and OVA-specific ELISA revealed that the bioactivity of the model protein was maintained during the manufacture of MNs. In hen\u2019s egg-chorioallantoic membrane test, MNs fabricated from all chosen polymers were classified as non-irritants. Furthermore, ex vivo permeation studies showed that optimised MNs could permeate 86.99\u2009\u00b1\u20097.37% of OVA through the sclera, twice that of the needle-free patch (42.16\u2009\u00b1\u20093.95%), highlighting the capability of MNs to circumvent physical barriers and promote protein delivery to the posterior segment of the eye. In this work, a novel, efficient and safe intraocular protein delivery system was successfully established.<\/jats:p>\n                <jats:p><jats:bold>Graphical abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s13346-022-01190-x","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T14:09:06Z","timestamp":1655474946000},"page":"2142-2158","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Rapidly dissolving bilayer microneedles enabling minimally invasive and efficient protein delivery to the posterior segment of the eye"],"prefix":"10.1007","volume":"13","author":[{"given":"Yu","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalitkumar K.","family":"Vora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan F.","family":"Donnelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7582-2082","authenticated-orcid":false,"given":"Thakur Raghu Raj","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"1190_CR1","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1080\/07853890600946724","volume":"38","author":"KM Gehrs","year":"2006","unstructured":"Gehrs KM, Anderson DH, Johnson LV, Hageman GS. Age-related macular degeneration - Emerging pathogenetic and therapeutic concepts. Ann Med. 2006;38:450\u201371.","journal-title":"Ann Med"},{"key":"1190_CR2","doi-asserted-by":"publisher","first-page":"711","DOI":"10.2147\/DDDT.S40215","volume":"7","author":"F Semeraro","year":"2013","unstructured":"Semeraro F, Morescalchi F, Duse S, Parmeggiani F, Gambicorti E, Costagliola C. Aflibercept in wet AMD: Specific role and optimal use. Drug Des Devel Ther. 2013;7:711\u201322.","journal-title":"Drug Des Devel Ther"},{"key":"1190_CR3","doi-asserted-by":"publisher","first-page":"1616","DOI":"10.1167\/iovs.12-10260","volume":"54","author":"L Xu","year":"2013","unstructured":"Xu L, Lu T, Tuomi L, Jumbe N, Lu J, Eppler S, et al. Pharmacokinetics of ranibizumab in patients with neovascular age-related macular degeneration: A population approach. Investig Ophthalmol Vis Sci. 2013;54:1616\u201324.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"1190_CR4","first-page":"263","volume":"1","author":"SA Vinores","year":"2006","unstructured":"Vinores SA. Pegaptanib in the treatment of wet, age-related macular degeneration. Int J Nanomedicine. 2006;1:263\u20138.","journal-title":"Int J Nanomedicine"},{"key":"1190_CR5","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1016\/j.drudis.2016.10.015","volume":"22","author":"K Radhakrishnan","year":"2017","unstructured":"Radhakrishnan K, Sonali N, Moreno M, Nirmal J, Fernandez AA, Venkatraman S, et al. Protein delivery to the back of the eye: barriers, carriers and stability of anti-VEGF proteins. Drug Discov Today Elsevier Ltd. 2017;22:416\u201323.","journal-title":"Drug Discov Today Elsevier Ltd"},{"key":"1190_CR6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s40199-015-0110-0","volume":"23","author":"S Dashti-Khavidaki","year":"2015","unstructured":"Dashti-Khavidaki S, Abdollahi M. Intravitreal administration of bevacizumab: Pros and cons. DARU, J Pharm Sci. 2015;23:15\u20138.","journal-title":"DARU, J Pharm Sci"},{"key":"1190_CR7","doi-asserted-by":"crossref","unstructured":"Luaces-Rodriguez A, Mondelo-Garcia C, Zarra-Ferro I, Gonzalez-Barcia M, Aguiar P, Fernandez-Ferreiro A, Otero-Espinar FJ (2020). Intravitreal anti-VEGF drug delivery systems for age-related macular degeneration. Int J Pharma 573:118767","DOI":"10.1016\/j.ijpharm.2019.118767"},{"key":"1190_CR8","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.jconrel.2017.10.005","volume":"265","author":"LK Vora","year":"2017","unstructured":"Vora LK, Donnelly RF, Larra\u00f1eta E, Gonz\u00e1lez-V\u00e1zquez P, Thakur RRS, Vavia PR. Novel bilayer dissolving microneedle arrays with concentrated PLGA nano-microparticles for targeted intradermal delivery: Proof of concept. J Control Release. 2017;265:93\u2013101.","journal-title":"J Control Release"},{"key":"1190_CR9","doi-asserted-by":"crossref","unstructured":"Tekko IA, Vora LK, Volpe\u2010Zanutto F, Moffatt K, Jarrahian C, McCarthy HO, Donnelly RF (2022) Novel bilayer microarray patch (MAP)-assisted long-acting micro-depot cabotegravir intradermal delivery for HIV pre-exposure prophylaxis (PrEP). Adv Mater 5:32\u201341","DOI":"10.1002\/adfm.202106999"},{"key":"1190_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mser.2016.03.001","volume":"104","author":"E Larra\u00f1eta","year":"2016","unstructured":"Larra\u00f1eta E, Lutton REM, Woolfson AD, Donnelly RF. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mater Sci Eng R Reports. 2016;104:1\u201332.","journal-title":"Mater Sci Eng R Reports"},{"key":"1190_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2021.112226","volume":"127","author":"K Peng","year":"2021","unstructured":"Peng K, Vora LK, Dom\u00ednguez-Robles J, Naser YA, Li M, Larra\u00f1eta E, et al. Hydrogel-forming microneedles for rapid and efficient skin deposition of controlled release tip-implants. Mater Sci Eng C [Internet]. 2021;127: 112226.","journal-title":"Mater Sci Eng C [Internet]"},{"key":"1190_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2020.120152","volume":"593","author":"\u00c1 C\u00e1rcamo-Mart\u00ednez","year":"2021","unstructured":"C\u00e1rcamo-Mart\u00ednez \u00c1, Mallon B, Anjani QK, Dom\u00ednguez-Robles J, Utomo E, Vora LK, et al. Enhancing intradermal delivery of tofacitinib citrate: Comparison between powder-loaded hollow microneedle arrays and dissolving microneedle arrays. Int J Pharm [Internet]. 2021;593: 120152.","journal-title":"Int J Pharm [Internet]"},{"key":"1190_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120455","volume":"599","author":"\u00c1 C\u00e1rcamo-Mart\u00ednez","year":"2021","unstructured":"C\u00e1rcamo-Mart\u00ednez \u00c1, Mallon B, Dom\u00ednguez-Robles J, Vora LK, Anjani QK, Donnelly RF. Hollow microneedles: A perspective in biomedical applications. Int J Pharm [Internet]. 2021;599: 120455.","journal-title":"Int J Pharm [Internet]"},{"key":"1190_CR14","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1080\/17425247.2016.1218460","volume":"14","author":"RR Thakur Singh","year":"2017","unstructured":"Thakur Singh RR, Tekko I, McAvoy K, McMillan H, Jones D, Donnelly RF. Minimally invasive microneedles for ocular drug delivery. Expert Opin Drug Deliv England. 2017;14:525\u201337.","journal-title":"Expert Opin Drug Deliv England"},{"key":"1190_CR15","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s11095-008-9756-3","volume":"26","author":"J Jiang","year":"2009","unstructured":"Jiang J, Moore JS, Edelhauser HF, Prausnitz MR. Intrascleral drug delivery to the eye using hollow microneedles. Pharm Res. 2009;26:395\u2013403.","journal-title":"Pharm Res"},{"key":"1190_CR16","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.06.002","volume":"175","author":"E McAlister","year":"2021","unstructured":"McAlister E, Kirkby M, Dom\u00ednguez-Robles J, Paredes AJ, Anjani QK, Moffatt K, et al. The role of microneedle arrays in drug delivery and patient monitoring to prevent diabetes induced fibrosis. Adv Drug Deliv Rev. 2021;175: 113825.","journal-title":"Adv Drug Deliv Rev"},{"key":"1190_CR17","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.ejpb.2020.12.006","volume":"159","author":"LK Vora","year":"2021","unstructured":"Vora LK, Moffatt K, Tekko IA, Paredes AJ, Volpe-Zanutto F, Mishra D, et al. Microneedle array systems for long-acting drug delivery. Eur J Pharm Biopharm. 2021;159:44\u201376.","journal-title":"Eur J Pharm Biopharm"},{"key":"1190_CR18","doi-asserted-by":"crossref","unstructured":"Paredes AJ, Volpe-Zanutto F, Dian Permana A, Murphy AJ, Picco CJ, Vora LK, et al. Novel tip-loaded dissolving and implantable microneedle array patches for sustained release of finasteride. Int J Pharm. 2021;120885.","DOI":"10.1016\/j.ijpharm.2021.120885"},{"key":"1190_CR19","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1002\/smll.201001091","volume":"7","author":"JW Lee","year":"2011","unstructured":"Lee JW, Choi SO, Felner EI, Prausnitz MR. Dissolving microneedle patch for transdermal delivery of human growth hormone. Small. 2011;7:531\u20139.","journal-title":"Small"},{"key":"1190_CR20","doi-asserted-by":"crossref","unstructured":"Larra\u00f1eta E, Vora L. Delivery of Nanomedicines Using Microneedles. Microneedles Drug Vaccine Deliv. Patient Monit. 2018. p. 177\u2013205.","DOI":"10.1002\/9781119305101.ch6"},{"key":"1190_CR21","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s13346-021-01107-0","volume":"12","author":"MI Nasiri","year":"2021","unstructured":"Nasiri MI, Vora LK, Ershaid JA, Peng K, Tekko IA, Donnelly RF. Nanoemulsion-based dissolving microneedle arrays for enhanced intradermal and transdermal delivery. Drug Deliv Transl Res. 2021;12:881\u201396.","journal-title":"Drug Deliv Transl Res"},{"key":"1190_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2022.100217","volume":"13","author":"AJ Paredes","year":"2022","unstructured":"Paredes AJ, Volpe-Zanutto F, Vora LK, Tekko IA, Permana AD, Picco CJ, et al. Systemic delivery of tenofovir alafenamide using dissolving and implantable microneedle patches. Mater Today Bio. 2022;13: 100217.","journal-title":"Mater Today Bio"},{"key":"1190_CR23","doi-asserted-by":"crossref","unstructured":"Ripolin A, Quinn J, Larra\u00f1eta E, Vicente-Perez EM, Barry J, Donnelly RF. Successful Application of Large Microneedle Patches by Human Volunteers. Int J Pharm. Elsevier BV\u00a02017;521:92\u2013101","DOI":"10.1016\/j.ijpharm.2017.02.011"},{"key":"1190_CR24","doi-asserted-by":"crossref","unstructured":"Li M, Vora LK, Peng K, Donnelly RF. Trilayer microneedle array assisted transdermal and intradermal delivery of dexamethasone. Int J Pharm. 2021;121295","DOI":"10.1016\/j.ijpharm.2021.121295"},{"key":"1190_CR25","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.ejpb.2021.04.024","volume":"165","author":"S Rojekar","year":"2021","unstructured":"Rojekar S, Vora LK, Tekko IA, Volpe-Zanutto F, McCarthy HO, Vavia PR, et al. Etravirine-loaded dissolving microneedle arrays for long-acting delivery. Eur J Pharm Biopharm Elsevier. 2021;165:41\u201351.","journal-title":"Eur J Pharm Biopharm Elsevier"},{"key":"1190_CR26","doi-asserted-by":"publisher","first-page":"20","DOI":"10.5301\/EJO.2010.6051","volume":"21","author":"N Fischer","year":"2011","unstructured":"Fischer N, Narayanan R, Loewenstein A, Kuppermann BD. Drug delivery to the posterior segment of the eye. Eur J Ophthalmol. 2011;21:20\u20136.","journal-title":"Eur J Ophthalmol"},{"key":"1190_CR27","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.jconrel.2021.10.001","volume":"339","author":"K Peng","year":"2021","unstructured":"Peng K, Vora LK, Tekko IA, Permana AD, Dom\u00ednguez-Robles J, Ramadon D, et al. Dissolving microneedle patches loaded with amphotericin B microparticles for localised and sustained intradermal delivery: Potential for enhanced treatment of cutaneous fungal infections. J Control Release. 2021;339:361\u201380.","journal-title":"J Control Release"},{"key":"1190_CR28","doi-asserted-by":"crossref","unstructured":"Vora LK, Courtenay AJ, Tekko IA, Larra\u00f1eta E, Donnelly RF. Pullulan-based dissolving microneedle arrays for enhanced transdermal delivery of small and large biomolecules. Int J Biol Macromol. Elsevier BV\u00a02020;146:290\u20138.","DOI":"10.1016\/j.ijbiomac.2019.12.184"},{"key":"1190_CR29","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.ejpb.2021.05.022","volume":"165","author":"Y Wu","year":"2021","unstructured":"Wu Y, Vora LK, Wang Y, Adrianto MF, Tekko IA, Waite D, et al. Long-acting nanoparticle-loaded bilayer microneedles for protein delivery to the posterior segment of the eye. Eur J Pharm Biopharm. 2021;165:306\u201318.","journal-title":"Eur J Pharm Biopharm"},{"key":"1190_CR30","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.coph.2017.07.007","volume":"36","author":"K Moffatt","year":"2017","unstructured":"Moffatt K, Wang Y, Raj Singh TR, Donnelly RF. Microneedles for enhanced transdermal and intraocular drug delivery. Curr Opin Pharmacol. 2017;36:14\u201321.","journal-title":"Curr Opin Pharmacol"},{"key":"1190_CR31","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1007\/s10439-015-1314-7","volume":"43","author":"CR Osswald","year":"2015","unstructured":"Osswald CR, Kang-Mieler JJ. Controlled and Extended Release of a Model Protein from a Microsphere-Hydrogel Drug Delivery System. Ann Biomed Eng. 2015;43:2609\u201317.","journal-title":"Ann Biomed Eng"},{"key":"1190_CR32","doi-asserted-by":"publisher","first-page":"308","DOI":"10.3390\/pharmaceutics11070308","volume":"11","author":"S Abdelghany","year":"2019","unstructured":"Abdelghany S, Tekko IA, Vora L, Larra\u00f1eta E, Permana AD, Donnelly RF. Nanosuspension-Based Dissolving Microneedle Arrays for Intradermal Delivery of Curcumin. Pharmaceutics. 2019;11:308.","journal-title":"Pharmaceutics"},{"key":"1190_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.121422","volume":"614","author":"E Altunta\u015f","year":"2022","unstructured":"Altunta\u015f E, Tekko IA, Vora LK, Kumar N, Brodsky R, Chevallier O, et al. Nestorone nanosuspension-loaded dissolving microneedles array patch: A promising novel approach for \u201con-demand\u201d hormonal female-controlled peritcoital contraception. Int J Pharm. 2022;614: 121422.","journal-title":"Int J Pharm"},{"key":"1190_CR34","doi-asserted-by":"crossref","unstructured":"Albadr AA, Tekko IA, Vora LK, Ali AA, Laverty G, Donnelly RF, et al. Rapidly dissolving microneedle patch of amphotericin B for intracorneal fungal infections. Drug Deliv Transl Res. United States; 2021;12(4):931\u2013943.","DOI":"10.1007\/s13346-021-01032-2"},{"key":"1190_CR35","unstructured":"Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). Recommended Test Method Protocol\u202f: Hen \u2019 s Egg Test \u2013 Chorioallantoic Membrane ( HET-CAM ) Test Method. ICCVAM Test Method Eval Rep. 2010;13:B30\u20138."},{"key":"1190_CR36","doi-asserted-by":"crossref","unstructured":"Rein-Weston A, Tekko I, Vora L, Jarrahian C, Spreen B, Scott T, et al. LB8. Microarray Patch Delivery of Long-Acting HIV PrEP and Contraception. Open Forum Infect Dis. Oxford University Press; 2019;6:S996\u2013S996.","DOI":"10.1093\/ofid\/ofz415.2491"},{"key":"1190_CR37","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.3390\/polym12081800","volume":"12","author":"P Snetkov","year":"2020","unstructured":"Snetkov P, Zakharova K, Morozkina S, Olekhnovich R, Uspenskaya M. Hyaluronic acid: The influence of molecular weight on structural, physical, physico-chemical, and degradable properties of biopolymer. Polymers (Basel). 2020;12:1800.","journal-title":"Polymers (Basel)"},{"issue":"6","key":"1190_CR38","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1007\/s13346-016-0332-9","volume":"6","author":"RRS Thakur","year":"2016","unstructured":"Thakur RRS, Tekko IA, Al-Shammari F, Ali AA, McCarthy H, Donnelly RF. Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery. Drug Deliv Transl Res. 2016;6(6):800\u201315.","journal-title":"Drug Deliv Transl Res"},{"key":"1190_CR39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpharm.2015.05.023","volume":"490","author":"B McKenzie","year":"2015","unstructured":"McKenzie B, Kay G, Matthews KH, Knott RM, Cairns D. The hen\u2019s egg chorioallantoic membrane (HET-CAM) test to predict the ophthalmic irritation potential of a cysteamine-containing gel: Quantification using Photoshop\u00ae and ImageJ. Int J Pharm. 2015;490:1\u20138.","journal-title":"Int J Pharm"},{"key":"1190_CR40","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1177\/1091581816672187","volume":"35","author":"A Batista-Duharte","year":"2016","unstructured":"Batista-Duharte A, Jorge Murillo G, P\u00e9rez UM, Tur EN, Portuondo DF, Mart\u00ednez BT, et al. The Hen\u2019s Egg Test on Chorioallantoic Membrane: An Alternative Assay for the Assessment of the Irritating Effect of Vaccine Adjuvants. Int J Toxicol. 2016;35:627\u201333.","journal-title":"Int J Toxicol"},{"key":"1190_CR41","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.2147\/DDDT.S115121","volume":"10","author":"S Yang","year":"2016","unstructured":"Yang S, Zhao J, Sun X. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: A comprehensive review. Drug Des Devel Ther. 2016;10:1857\u201367.","journal-title":"Drug Des Devel Ther"},{"key":"1190_CR42","first-page":"464","volume":"55","author":"CR Osswald","year":"2014","unstructured":"Osswald CR, Kang Mieler JJ. Ovalbumin as a model protein for ranibizumab in a poly(lactic-co-glycolic) acid microsphere drug delivery system. Invest Ophthalmol Vis Sci. 2014;55:464.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"1190_CR43","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1089\/jop.2009.0059","volume":"26","author":"ER Rieke","year":"2010","unstructured":"Rieke ER, Amaral J, Becerra SP, Lutz RJ. Sustained subconjunctival protein delivery using a thermosetting gel delivery system. J Ocul Pharmacol Ther. 2010;26:55\u201364.","journal-title":"J Ocul Pharmacol Ther"},{"key":"1190_CR44","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1111\/jphp.12248","volume":"67","author":"MTC McCrudden","year":"2015","unstructured":"McCrudden MTC, Torrisi BM, Al-Zahrani S, McCrudden CM, Zaric M, Scott CJ, et al. Laser-engineered dissolving microneedle arrays for protein delivery: Potential for enhanced intradermal vaccination. J Pharm Pharmacol. 2015;67:409\u201325.","journal-title":"J Pharm Pharmacol"},{"key":"1190_CR45","doi-asserted-by":"crossref","unstructured":"Rodgers AM, Courtenay AJ, Donnelly RF. Dissolving microneedles for intradermal vaccination: manufacture, formulation, and stakeholder considerations. Expert Opin Drug Deliv. Taylor & Francis; 2018;15:1039\u201343.","DOI":"10.1080\/17425247.2018.1522301"},{"key":"1190_CR46","first-page":"2529","volume":"43","author":"TW Olsen","year":"2002","unstructured":"Olsen TW, Sanderson S, Feng X, Hubbard WC. Porcine sclera: Thickness and surface area. Investig Ophthalmol Vis Sci. 2002;43:2529\u201332.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"1190_CR47","first-page":"259","volume":"15","author":"S Nicoli","year":"2009","unstructured":"Nicoli S, Ferrari G, Quarta M, Macaluso C, Govoni P, Dallatana D, et al. Porcine sclera as a model of human sclera for in vitro transport experiments: histology, SEM, and comparative permeability. Mol Vis. 2009;15:259\u201366.","journal-title":"Mol Vis"},{"key":"1190_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2019.118808","volume":"572","author":"G Roy","year":"2019","unstructured":"Roy G, Galigama RD, Thorat VS, Mallela LS, Roy S, Garg P, et al. Amphotericin B containing microneedle ocular patch for effective treatment of fungal keratitis. Int J Pharm. 2019;572: 118808.","journal-title":"Int J Pharm"},{"key":"1190_CR49","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1080\/02713683.2017.1418893","volume":"43","author":"C Gagliano","year":"2018","unstructured":"Gagliano C, Papa V, Amato R, Malaguarnera G, Avitabile T. Measurement of the Retention Time of Different Ophthalmic Formulations with Ultrahigh-Resolution Optical Coherence Tomography. Curr Eye Res Taylor & Francis. 2018;43:499\u2013502.","journal-title":"Curr Eye Res Taylor & Francis"}],"container-title":["Drug Delivery and Translational Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-022-01190-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13346-022-01190-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13346-022-01190-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,2]],"date-time":"2023-07-02T21:01:37Z","timestamp":1688331697000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13346-022-01190-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,17]]},"references-count":49,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["1190"],"URL":"https:\/\/doi.org\/10.1007\/s13346-022-01190-x","relation":{},"ISSN":["2190-393X","2190-3948"],"issn-type":[{"value":"2190-393X","type":"print"},{"value":"2190-3948","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,17]]},"assertion":[{"value":"24 May 2022","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2022","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed without use of animals and human volunteers. Therefore, this is not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human and animal participants"}},{"value":"All the authors provided consent for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Thakur Raghu Raj Singh is an inventor of patents and founder of Re-Vana Therapeutics Ltd. The resulting potential conflict of interest has been disclosed and is managed by Queen's University Belfast. The companies had no role in the design of the manuscript, in the collection, analyses or interpretation of the various studies reviewed, in the writing of the manuscript. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}