{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:18:01Z","timestamp":1776795481914,"version":"3.51.2"},"reference-count":66,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001607","name":"Eye and Ear Foundation of Pittsburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001607","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["5T32EY017271"],"award-info":[{"award-number":["5T32EY017271"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY008098"],"award-info":[{"award-number":["P30EY008098"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Unrestricted Grant"],"award-info":[{"award-number":["Unrestricted Grant"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Current systems for topical ocular drug delivery enable non-invasive administration of therapeutics to the eye but suffer from poor permeability and bioavailability, limiting therapeutic efficacy. Metal-organic frameworks are porous, crystalline materials that can serve as drug delivery systems and may improve these shortcomings. In this study, we explore the use of ZIF-8 as a representative metal-organic framework for topical ocular drug delivery. ZIF-8 particles were prepared via a simplified aqueous synthetic method and loaded with ovalbumin, a model molecule to simulate anti-angiogenic proteins that are used to treat retinal diseases. The physical properties of unloaded and loaded ZIF-8 were evaluated with a variety of spectroscopic, imaging, and desorption techniques that confirmed successful loading with ovalbumin (&gt;46% loading capacity) without severe disruption to the structure of ZIF-8. In bulk solution, loaded ovalbumin is gradually released in a linear fashion for up to 60 days. Loaded ZIF-8 applied to chicken eggs or bovine eyes showed minimal to no levels of irritation, supporting our hypothesis that ZIF-8 can be safely applied to ocular tissue. When applied to ex vivo bovine eyes, loaded agents administered in ZIF-8 penetrate the sclera, suggesting ZIF-8 may enhance permeability to intraocular tissue. These results highlight the potential of ZIF-8 as a carrier in topical ocular delivery systems and provide a crucial foundation to evaluate their efficacy in topical ocular drug delivery using in vivo models.<\/jats:p>","DOI":"10.1371\/journal.pone.0346473","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:22:46Z","timestamp":1776792166000},"page":"e0346473","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Zeolitic imidazolate frameworks (ZIF-8) as a carrier in a topical ocular delivery system for the treatment of ocular diseases"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1251-3845","authenticated-orcid":true,"given":"Phillip A.","family":"Harding","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James H.","family":"Westbay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ethan","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8949-8305","authenticated-orcid":true,"given":"Morgan V.","family":"DiLeo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"issue":"1","key":"pone.0346473.ref001","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3390\/pharmaceutics13010108","article-title":"Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives","volume":"13","author":"HM Kim","year":"2021","journal-title":"Pharmaceutics"},{"key":"pone.0346473.ref002","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jconrel.2023.07.055","article-title":"Challenges and strategies for ocular posterior diseases therapy via non-invasive advanced drug delivery","volume":"361","author":"Q Qi","year":"2023","journal-title":"J Control Release"},{"issue":"1","key":"pone.0346473.ref003","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3390\/pharmaceutics15010205","article-title":"Ocular delivery of therapeutic proteins: a review","volume":"15","author":"DH Shastri","year":"2023","journal-title":"Pharmaceutics"},{"issue":"3","key":"pone.0346473.ref004","doi-asserted-by":"crossref","first-page":"269","DOI":"10.3390\/pharmaceutics12030269","article-title":"Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations","volume":"12","author":"R Varela-Fern\u00e1ndez","year":"2020","journal-title":"Pharmaceutics"},{"issue":"7","key":"pone.0346473.ref005","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/eye.2013.107","article-title":"Adverse events and complications associated with intravitreal injection of anti-VEGF agents: a review of literature","volume":"27","author":"KG Falavarjani","year":"2013","journal-title":"Eye (Lond)"},{"issue":"7","key":"pone.0346473.ref006","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.jfo.2014.11.015","article-title":"Ranibizumab for exudative age-related macular degeneration: A five year study of adherence to follow-up in a real-life setting","volume":"38","author":"E Boulanger-Scemama","year":"2015","journal-title":"J Fr Ophtalmol"},{"issue":"1","key":"pone.0346473.ref007","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s13643-023-02261-x","article-title":"Non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy: a systematic review and meta-analysis","volume":"12","author":"H Shahzad","year":"2023","journal-title":"Syst Rev"},{"issue":"3","key":"pone.0346473.ref008","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1208\/s12248-010-9183-3","article-title":"Ocular drug delivery","volume":"12","author":"R Gaudana","year":"2010","journal-title":"AAPS J"},{"issue":"2","key":"pone.0346473.ref009","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1208\/s12249-023-02516-9","article-title":"Ocular drug delivery: a comprehensive review","volume":"24","author":"S Ahmed","year":"2023","journal-title":"AAPS PharmSciTech"},{"issue":"8","key":"pone.0346473.ref010","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.3390\/ijms23084458","article-title":"Applications of Metal-Organic Frameworks as Drug Delivery Systems","volume":"23","author":"B Maranescu","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"16","key":"pone.0346473.ref011","doi-asserted-by":"crossref","first-page":"11739","DOI":"10.1021\/acs.inorgchem.1c00538","article-title":"Breast cancer targeting of a drug delivery system through postsynthetic modification of curcumin@N(3)-bio-MOF-100 via click chemistry","volume":"60","author":"RC Alves","year":"2021","journal-title":"Inorg Chem"},{"issue":"1","key":"pone.0346473.ref012","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1517\/17425247.2013.741583","article-title":"Metal-organic frameworks as potential drug delivery systems","volume":"10","author":"C-Y Sun","year":"2013","journal-title":"Expert Opin Drug Deliv"},{"issue":"36","key":"pone.0346473.ref013","doi-asserted-by":"crossref","first-page":"5974","DOI":"10.1002\/anie.200601878","article-title":"Metal-organic frameworks as efficient materials for drug delivery","volume":"45","author":"P Horcajada","year":"2006","journal-title":"Angew Chem Int Ed Engl"},{"issue":"37","key":"pone.0346473.ref014","article-title":"Nanoscale Metal-Organic Frameworks for Therapeutic, Imaging, and Sensing Applications","volume":"30","author":"K Lu","year":"2018","journal-title":"Adv Mater"},{"key":"pone.0346473.ref015","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.biomaterials.2017.01.025","article-title":"Positioning metal-organic framework nanoparticles within the context of drug delivery - A comparison with mesoporous silica nanoparticles and dendrimers","volume":"123","author":"S Wuttke","year":"2017","journal-title":"Biomaterials"},{"issue":"6","key":"pone.0346473.ref016","doi-asserted-by":"crossref","first-page":"7004","DOI":"10.1021\/acsami.1c01089","article-title":"Metal-Organic Frameworks for Drug Delivery: A Design Perspective","volume":"13","author":"HD Lawson","year":"2021","journal-title":"ACS Appl Mater Interfaces"},{"issue":"2","key":"pone.0346473.ref017","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11705-020-1927-8","article-title":"Zeolitic imidazolate framework-8 (ZIF-8) for drug delivery: A critical review","volume":"15","author":"S Feng","year":"2020","journal-title":"Front Chem Sci Eng"},{"issue":"1","key":"pone.0346473.ref018","doi-asserted-by":"crossref","first-page":"16815","DOI":"10.1038\/s41598-020-73848-w","article-title":"ZIF-8 as a promising drug delivery system for benznidazole: development, characterization, in vitro dialysis release and cytotoxicity","volume":"10","author":"LR de Moura Ferraz","year":"2020","journal-title":"Sci Rep"},{"issue":"40","key":"pone.0346473.ref019","doi-asserted-by":"crossref","first-page":"16811","DOI":"10.1039\/C4TA02984D","article-title":"Zeolitic imidazolate framework materials: recent progress in synthesis and applications","volume":"2","author":"B Chen","year":"2014","journal-title":"J Mater Chem A"},{"issue":"13","key":"pone.0346473.ref020","doi-asserted-by":"crossref","first-page":"3941","DOI":"10.1039\/D4NA01015A","article-title":"Synthesis methods, structure, and recent trends of ZIF-8-based materials in the biomedical field","volume":"7","author":"TV Tran","year":"2025","journal-title":"Nanoscale Adv"},{"key":"pone.0346473.ref021","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.cej.2015.02.094","article-title":"ZIF-8: A comparison of synthesis methods","volume":"271","author":"YR Lee","year":"2015","journal-title":"Chem Eng J"},{"issue":"2","key":"pone.0346473.ref022","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1021\/acsami.8b20222","article-title":"Metal-Organic Frameworks as Drug Delivery Platforms for Ocular Therapeutics","volume":"11","author":"J Gandara-Loe","year":"2019","journal-title":"ACS Appl Mater Interfaces"},{"key":"pone.0346473.ref023","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.actbio.2018.08.023","article-title":"Metal-organic frameworks, NH2-MIL-88(Fe), as carriers for ophthalmic delivery of brimonidine","volume":"79","author":"S-N Kim","year":"2018","journal-title":"Acta Biomater"},{"issue":"27","key":"pone.0346473.ref024","doi-asserted-by":"crossref","first-page":"30189","DOI":"10.1021\/acsami.0c07517","article-title":"MOF-Based Polymeric Nanocomposite Films as Potential Materials for Drug Delivery Devices in Ocular Therapeutics","volume":"12","author":"J Gandara-Loe","year":"2020","journal-title":"ACS Appl Mater Interfaces"},{"issue":"6","key":"pone.0346473.ref025","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2023.e17488","article-title":"Advances in drug delivery systems, challenges and future directions","volume":"9","author":"TC Ezike","year":"2023","journal-title":"Heliyon"},{"key":"pone.0346473.ref026","doi-asserted-by":"crossref","first-page":"148576","DOI":"10.1016\/j.cej.2024.148576","article-title":"A facile method to construct ZIF-8 MOFs on contact lens for high antibiotics loading and self-defensive release","volume":"481","author":"Y Shao","year":"2024","journal-title":"Chem Eng J"},{"key":"pone.0346473.ref027","doi-asserted-by":"crossref","first-page":"11163","DOI":"10.2147\/IJN.S480800","article-title":"Zeolitic Imidazolate Framework-8 Offers an Anti-Inflammatory and Antifungal Method in the Treatment of Aspergillus Fungal Keratitis in vitro and in vivo","volume":"19","author":"X Fu","year":"2024","journal-title":"Int J Nanomedicine"},{"issue":"7","key":"pone.0346473.ref028","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1039\/c0cc05002d","article-title":"Rapid synthesis of zeolitic imidazolate framework-8 (ZIF-8) nanocrystals in an aqueous system","volume":"47","author":"Y Pan","year":"2011","journal-title":"Chem Commun (Camb)"},{"key":"pone.0346473.ref029","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ejpb.2023.04.012","article-title":"Ocular permeability, intraocular biodistribution of lipid nanocapsule formulation intended for retinal drug delivery","volume":"187","author":"G Christensen","year":"2023","journal-title":"Eur J Pharm Biopharm"},{"issue":"5","key":"pone.0346473.ref030","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.ejps.2012.03.013","article-title":"Ex vivo models to evaluate the role of ocular melanin in trans-scleral drug delivery","volume":"46","author":"S Pescina","year":"2012","journal-title":"Eur J Pharm Sci"},{"issue":"1","key":"pone.0346473.ref031","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejpb.2014.04.018","article-title":"In vitro permeability of a model protein across ocular tissues and effect of iontophoresis on the transscleral delivery","volume":"88","author":"E Tratta","year":"2014","journal-title":"Eur J Pharm Biopharm"},{"issue":"3","key":"pone.0346473.ref032","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1021\/acs.chemrev.0c00487","article-title":"Power of Infrared and Raman Spectroscopies to Characterize Metal-Organic Frameworks and Investigate Their Interaction with Guest Molecules","volume":"121","author":"KI Hadjiivanov","year":"2021","journal-title":"Chem Rev"},{"issue":"21","key":"pone.0346473.ref033","doi-asserted-by":"crossref","first-page":"27887","DOI":"10.1021\/acsami.4c02396","article-title":"ZIF-8 Vibrational Spectra: Peak Assignments and Defect Signals","volume":"16","author":"M Ahmad","year":"2024","journal-title":"ACS Appl Mater Interfaces"},{"key":"pone.0346473.ref034","doi-asserted-by":"crossref","first-page":"101366","DOI":"10.1016\/j.mtchem.2022.101366","article-title":"Enhancement of the intrinsic fluorescence of ZIF-8 via post-synthetic cation exchange with Cd2+ and its incorporation into PDMS films for selective sulfide optical sensing","volume":"28","author":"FG Moscoso","year":"2023","journal-title":"Materials Today Chemistry"},{"key":"pone.0346473.ref035","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.micromeso.2016.07.008","article-title":"Innovative layer by layer and continuous growth methods for synthesis of ZIF-8 membrane on porous polymeric support using poly(ether- block -amide) as structure directing agent for gas separation","volume":"234","author":"A Jomekian","year":"2016","journal-title":"Micropor Mesopor Mat"},{"issue":"27","key":"pone.0346473.ref036","doi-asserted-by":"crossref","first-page":"8552","DOI":"10.1021\/ja071174k","article-title":"Applicability of the BET method for determining surface areas of microporous metal-organic frameworks","volume":"129","author":"KS Walton","year":"2007","journal-title":"J Am Chem Soc"},{"issue":"31","key":"pone.0346473.ref037","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1039\/C9CE00757A","article-title":"Degradation of ZIF-8 in phosphate buffered saline media","volume":"21","author":"J Vel\u00e1squez-Hern\u00e1ndez M de","year":"2019","journal-title":"CrystEngComm"},{"issue":"3","key":"pone.0346473.ref038","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1021\/jacs.5b11720","article-title":"One-pot Synthesis of Metal-Organic Frameworks with Encapsulated Target Molecules and Their Applications for Controlled Drug Delivery","volume":"138","author":"H Zheng","year":"2016","journal-title":"J Am Chem Soc"},{"key":"pone.0346473.ref039","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jddst.2017.07.004","article-title":"Synthesis and characterization of ZIF-8 nanoparticles for controlled release of 6-mercaptopurine drug","volume":"41","author":"H Kaur","year":"2017","journal-title":"Journal of Drug Delivery Science and Technology"},{"key":"pone.0346473.ref040","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0278-6915(86)90099-2","article-title":"The HET-CAM test: An alternative to the draize eye test","volume":"24","author":"NP Luepke","year":"1986","journal-title":"Food and Chemical Toxicology"},{"issue":"3","key":"pone.0346473.ref041","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/0272-0590(92)90142-5","article-title":"Bovine corneal opacity and permeability test: an in vitro assay of ocular irritancy","volume":"18","author":"P Gautheron","year":"1992","journal-title":"Fundam Appl Toxicol"},{"key":"pone.0346473.ref042","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.micromeso.2018.12.035","article-title":"Stability of ZIF-8 in water under ambient conditions","volume":"279","author":"H Zhang","year":"2019","journal-title":"Micropor Mesopor Mat"},{"issue":"8","key":"pone.0346473.ref043","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1080\/10610278.2019.1616089","article-title":"ZIF-8 Degrades in Cell Media, Serum, and Some-But Not All-Common Laboratory Buffers","volume":"31","author":"MA Luzuriaga","year":"2019","journal-title":"Supramolecular Chemistry"},{"issue":"55","key":"pone.0346473.ref044","doi-asserted-by":"crossref","first-page":"31471","DOI":"10.1039\/C8RA06414H","article-title":"Synthesis of zeolitic imidazolate framework-8 on polyester fiber for PM2.5 removal","volume":"8","author":"Y Zhang","year":"2018","journal-title":"RSC Adv"},{"issue":"12","key":"pone.0346473.ref045","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.1039\/D3MH00717K","article-title":"Dynamic light scattering and transmission electron microscopy in drug delivery: a roadmap for correct characterization of nanoparticles and interpretation of results","volume":"10","author":"SK Filippov","year":"2023","journal-title":"Mater Horiz"},{"key":"pone.0346473.ref046","first-page":"150","article-title":"Effect of circulation on the disposition and ocular tissue distribution of 20 nm nanoparticles after periocular administration","volume":"14","author":"AC Amrite","year":"2008","journal-title":"Mol Vis"},{"issue":"12","key":"pone.0346473.ref047","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1211\/jpp.57.12.0005","article-title":"Size-dependent disposition of nanoparticles and microparticles following subconjunctival administration","volume":"57","author":"AC Amrite","year":"2005","journal-title":"J Pharm Pharmacol"},{"issue":"47","key":"pone.0346473.ref048","doi-asserted-by":"crossref","first-page":"44601","DOI":"10.1021\/acsomega.3c04973","article-title":"Degradation kinetic studies of BSA@ZIF-8 nanoparticles with various zinc precursors, metal-to-ligand ratios, and pH conditions","volume":"8","author":"J Gao","year":"2023","journal-title":"ACS Omega"},{"issue":"62","key":"pone.0346473.ref049","doi-asserted-by":"crossref","first-page":"39169","DOI":"10.1039\/D1RA07089D","article-title":"Degradation kinetic study of ZIF-8 microcrystals with and without the presence of lactic acid","volume":"11","author":"SA Butonova","year":"2021","journal-title":"RSC Adv"},{"key":"pone.0346473.ref050","doi-asserted-by":"crossref","first-page":"109101","DOI":"10.1016\/j.exer.2022.109101","article-title":"Biochemistry of human tear film: A review","volume":"220","author":"S Masoudi","year":"2022","journal-title":"Exp Eye Res"},{"key":"pone.0346473.ref051","doi-asserted-by":"crossref","first-page":"108115","DOI":"10.1016\/j.exer.2020.108115","article-title":"Biological functions of tear film","volume":"197","author":"SC Pflugfelder","year":"2020","journal-title":"Exp Eye Res"},{"issue":"2","key":"pone.0346473.ref052","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1001\/archopht.1981.03930010303017","article-title":"Normal human tear pH by direct measurement","volume":"99","author":"MB Abelson","year":"1981","journal-title":"Arch Ophthalmol"},{"issue":"12","key":"pone.0346473.ref053","doi-asserted-by":"crossref","first-page":"6245","DOI":"10.1021\/acs.molpharmaceut.4c00686","article-title":"New Insights on the Burst Release Kinetics of Spray-Dried PLGA Microspheres","volume":"21","author":"K Michaelides","year":"2024","journal-title":"Mol Pharm"},{"issue":"11","key":"pone.0346473.ref054","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.1021\/acsbiomaterials.0c01228","article-title":"Phenomenology of the Initial Burst Release of Drugs from PLGA Microparticles","volume":"6","author":"J Yoo","year":"2020","journal-title":"ACS Biomater Sci Eng"},{"issue":"21","key":"pone.0346473.ref055","doi-asserted-by":"crossref","first-page":"5774","DOI":"10.1039\/D3SC00500C","article-title":"In vivo biocompatibility of ZIF-8 for slow release via intranasal administration","volume":"14","author":"S Kumari","year":"2023","journal-title":"Chem Sci"},{"key":"pone.0346473.ref056","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.biomaterials.2018.02.022","article-title":"Biocompatible and biodegradable zeolitic imidazolate framework\/polydopamine nanocarriers for dual stimulus triggered tumor thermo-chemotherapy","volume":"162","author":"Q Wu","year":"2018","journal-title":"Biomaterials"},{"issue":"25","key":"pone.0346473.ref057","doi-asserted-by":"crossref","first-page":"9437","DOI":"10.1039\/c2ra21087h","article-title":"Cytotoxicity and slow release of the anti-cancer drug doxorubicin from ZIF-8","volume":"2","author":"IB Vasconcelos","year":"2012","journal-title":"RSC Adv"},{"issue":"39","key":"pone.0346473.ref058","doi-asserted-by":"crossref","first-page":"12962","DOI":"10.1021\/acssuschemeng.2c04467","article-title":"Classically Synthesized ZIF-8 and Au\/ZIF-8 for Biocompatibility Assessment with Hemoglobin","volume":"10","author":"K Chaudhary","year":"2022","journal-title":"ACS Sustainable Chem Eng"},{"key":"pone.0346473.ref059","doi-asserted-by":"crossref","first-page":"1386534","DOI":"10.3389\/fbioe.2024.1386534","article-title":"Zeolitic imidazolate framework-8: a versatile nanoplatform for tissue regeneration","volume":"12","author":"Z Li","year":"2024","journal-title":"Front Bioeng Biotechnol"},{"issue":"5","key":"pone.0346473.ref060","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1097\/ACI.0b013e32834a95c9","article-title":"Ocular surface damage by ophthalmic compounds","volume":"11","author":"F Mantelli","year":"2011","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"pone.0346473.ref061","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S0891-5849(98)00253-6","article-title":"Zinc protects against oxidative damage in cultured human retinal pigment epithelial cells","volume":"26","author":"Jr Tate DJ","year":"1999","journal-title":"Free Radic Biol Med"},{"issue":"6","key":"pone.0346473.ref062","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1089\/jop.2016.0194","article-title":"The Effect of Tear Supplementation with 0.15% Preservative-Free Zinc-Hyaluronate on Ocular Surface Sensations in Patients with Dry Eye","volume":"33","author":"K Per\u00e9nyi","year":"2017","journal-title":"Journal of Ocular Pharmacology and Therapeutics"},{"key":"pone.0346473.ref063","first-page":"259","article-title":"Porcine sclera as a model of human sclera for in vitro transport experiments: histology, SEM, and comparative permeability","volume":"15","author":"S Nicoli","year":"2009","journal-title":"Mol Vis"},{"issue":"5","key":"pone.0346473.ref064","first-page":"1181","article-title":"Diffusion of high molecular weight compounds through sclera","volume":"41","author":"J Ambati","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"5","key":"pone.0346473.ref065","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1080\/17425247.2016.1227783","article-title":"Recent perspectives on the delivery of biologics to back of the eye","volume":"14","author":"M Joseph","year":"2017","journal-title":"Expert Opin Drug Deliv"},{"issue":"8","key":"pone.0346473.ref066","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1039\/D2TB02361J","article-title":"ZIF-8 integrated with polydopamine coating as a novel nano-platform for skin-specific drug delivery","volume":"11","author":"Q Wang","year":"2023","journal-title":"J Mater Chem B"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T17:22:55Z","timestamp":1776792175000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0346473"}},"subtitle":[],"editor":[{"given":"Safdar Ali","family":"Amur","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":66,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0346473","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]}}}