{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:56:51Z","timestamp":1775566611901,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Ocular diseases pose significant therapeutic challenges due to the eye\u2019s intricate anatomy and efficient physiological clearance mechanisms, which result in the rapid elimination of topically administered drugs and an overall bioavailability of less than 5%. Anterior segment disorders\u2014including keratitis, glaucoma, and dry eye syndrome\u2014account for the majority of ophthalmic conditions and are primarily managed with pharmacological agents. However, due to extremely low drug bioavailability and poor patient compliance, their therapeutic outcomes often result in a decreased disease control rate or require early surgical interventions. Nebulized drug delivery, particularly employing advanced vibrating mesh technology, has emerged as a promising strategy to overcome these limitations. By converting liquid formulations into a uniform aerosol of micron-sized (1\u201310 \u03bcm) droplets, this approach achieves extensive and consistent coverage of the ocular surface, increases the absorption contact area, prolongs drug residence time, and ultimately enhances drug bioavailability. Preliminary clinical evidence indicates that nebulized therapies outperform traditional eye drops by achieving higher drug concentrations in the aqueous humor and demonstrating superior pharmacodynamic profiles and patient tolerability\u2014particularly in conditions such as dry eye syndrome and glaucoma. This review presents a comprehensive overview of the mechanistic principles, technological advancements, and translational applications of nebulization-based ocular drug delivery systems. We place special emphasis on the integration of next-generation platforms that incorporate microelectromechanical systems (MEMS) and intelligent sensing technologies, enabling precision medicine approaches tailored to individual ocular pathophysiological characteristics. By bridging biomedical engineering and clinical ophthalmology, these innovations not only optimize existing therapeutic regimens but also pave the way for non-invasive delivery of complex biologics and gene therapies\u2014potentially reshaping the landscape of anterior segment drug delivery.<\/jats:p>","DOI":"10.3390\/pharmaceutics18040404","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:05:49Z","timestamp":1775563549000},"page":"404","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recent Achievements and Perspectives in Nebulization Devices for Anterior Segment Disease Treatment"],"prefix":"10.3390","volume":"18","author":[{"given":"Hongru","family":"Liu","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences, Hunan University, Changsha 410082, China"},{"name":"Greater Bay Area Institute for Innovation, Hunan University, Guangzhou 511300, China"},{"name":"Shenzhen Shuimu Biopharmaceutical Co., Ltd., Shenzhen 518126, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qibin","family":"Deng","sequence":"additional","affiliation":[{"name":"Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Hunan University, Changsha 410082, China"},{"name":"Greater Bay Area Institute for Innovation, Hunan University, Guangzhou 511300, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Hunan University, Changsha 410082, China"},{"name":"Greater Bay Area Institute for Innovation, Hunan University, Guangzhou 511300, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junxi","family":"Chen","sequence":"additional","affiliation":[{"name":"Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Xiong","sequence":"additional","affiliation":[{"name":"Shenzhen Shuimu Biopharmaceutical Co., Ltd., Shenzhen 518126, China"},{"name":"Nanfang Hospital, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e489","DOI":"10.1016\/S2214-109X(20)30488-5","article-title":"The Lancet Global Health Commission on Global Eye Health: Vision beyond 2020","volume":"9","author":"Burton","year":"2021","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Del Amo Eva, M. (2022). Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?. Front. Drug Deliv., 2.","DOI":"10.3389\/fddev.2022.954771"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2015.07.001","article-title":"Corneal structure and transparency","volume":"49","author":"Meek","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Liu, L.-C., Chen, Y.-H., and Lu, D.-W. (2023). Overview of Recent Advances in Nano-Based Ocular Drug Delivery. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242015352"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0169-409X(01)00193-4","article-title":"Transscleral drug delivery for posterior segment disease","volume":"52","author":"Geroski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.survophthal.2022.01.010","article-title":"Metabolomics and lipidomics approaches in human tears: A systematic review","volume":"67","author":"Khanna","year":"2022","journal-title":"Surv. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"108115","DOI":"10.1016\/j.exer.2020.108115","article-title":"Biological functions of tear film","volume":"197","author":"Pflugfelder","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_8","unstructured":"Chang, A.Y., and Purt, B. (2021). Biochemistry, tear film. StatPearls, StatPearls Publishing."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1080\/17425247.2020.1787983","article-title":"Commercialization challenges for drug eluting contact lenses","volume":"17","author":"Lanier","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"120924","DOI":"10.1016\/j.ijpharm.2021.120924","article-title":"Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies","volume":"607","author":"Mofidfar","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jps.2600680606","article-title":"Mechanistic and quantitative evaluation of precorneal pilocarpine disposition in albino rabbits","volume":"68","author":"Lee","year":"1979","journal-title":"J. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.5497\/wjp.v2.i2.47","article-title":"Ocular drug delivery systems: An overview","volume":"2","author":"Patel","year":"2013","journal-title":"World J. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1089\/jamp.2024.29116.mk","article-title":"New Generation Nebulizers","volume":"37","author":"Knoch","year":"2024","journal-title":"J. Aerosol Med. Pulm. Drug Deliv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1167\/iovs.65.11.28","article-title":"Mathematical Models of Ocular Drug Delivery","volume":"65","author":"Sadeghi","year":"2024","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120332","DOI":"10.1016\/j.ijpharm.2021.120332","article-title":"Topical drug delivery to the posterior segment of the eye: Thermodynamic considerations","volume":"597","author":"Sripetch","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/j.1442-9071.2005.01030.x","article-title":"Bioavailability of vitamin B12 using a small-volume nebulizer ophthalmic drug delivery system","volume":"33","author":"Kahn","year":"2005","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5152\/ejp.2014.00087","article-title":"Jet, Ultrasonic, and Mesh Nebulizers: An Evaluation of Nebulizers for Better Clinical Outcomes","volume":"16","author":"Ari","year":"2014","journal-title":"Eurasian J. Pulmonol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1177\/002013240204701103","article-title":"Design principles of liquid nebulization devices currently in use","volume":"47","author":"Rau","year":"2002","journal-title":"Discuss. Respir. Care"},{"key":"ref_19","unstructured":"Tservistas, M., and Fuchs, C. (2025, December 06). Principles of Nebulizer Technology. Available online: https:\/\/www.inhalationmag.com\/article\/principles-nebulizer-technology\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.4187\/respcare.07639","article-title":"Comparison of Vibrating Mesh, Jet, and Breath-Enhanced Nebulizers During Mechanical Ventilation","volume":"65","author":"Ashraf","year":"2020","journal-title":"Respir. Care"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ehrmann, S. (2018). Vibrating Mesh Nebulisers\u2014Can Greater Drug Delivery to the Airways and Lungs Improve Respiratory Outcomes?. Eur. Respir. Pulm. Dis., 4.","DOI":"10.17925\/ERPD.2018.4.1.33"},{"key":"ref_22","first-page":"310","article-title":"The effect of nebulized dorzolamide\/timolol fixed combination mist versus drops on retrobulbar blood flow and intraocular pressure in glaucoma patients","volume":"49","year":"2013","journal-title":"Medicina"},{"key":"ref_23","first-page":"107","article-title":"Dry eye disease. A review","volume":"77","year":"2021","journal-title":"Czech Slovak Ophtalmol."},{"key":"ref_24","first-page":"71","article-title":"The pathophysiology, diagnosis, and treatment of dry eye disease","volume":"112","author":"Messmer","year":"2015","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.2147\/DDDT.S203464","article-title":"A new approach of ocular nebulization with vitamin B12 versus oxytocin for the treatment of dry eye disease: An in vivo confocal microscopy study","volume":"13","author":"Yang","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.ophtha.2017.05.012","article-title":"Update on the Management of Infectious Keratitis","volume":"124","author":"Austin","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jtos.2021.12.001","article-title":"Fungal keratitis: A review of clinical presentations, treatment strategies and outcomes","volume":"24","author":"Sharma","year":"2022","journal-title":"Ocul. Surf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1167\/tvst.9.3.13","article-title":"Evaluation of Toluidine Blue-Mediated Photodynamic Therapy for Experimental Bacterial Keratitis in Rabbits","volume":"9","author":"Su","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.1167\/iovs.12-11509","article-title":"Collagen Cross-Linking Using Rose Bengal and Green Light to Increase Corneal Stiffness","volume":"54","author":"Cherfan","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1378\/chest.93.4.739","article-title":"The Effect of Nebulized Bronchodilator Therapy on Intraocular Pressures in Patients with Glaucoma","volume":"93","author":"Kalra","year":"1988","journal-title":"Chest"},{"key":"ref_31","unstructured":"Apstar (2025, December 06). Kolibri\u2014The Digital Mesh Nebulizer System for Inhaled Drug Delivery. Available online: https:\/\/aptar.com\/products\/pharmaceutical\/kolibri-nebulizer-soft-mist-inhaler\/."},{"key":"ref_32","first-page":"22","article-title":"Advancements in Monitoring Adherence\u2013A Smart Mesh Nebuliser","volume":"141","author":"Hsu","year":"2022","journal-title":"ONdrugDelivery"},{"key":"ref_33","unstructured":"Nebulizers, J. (2025, December 06). Smart Mesh Nebulizer by Briutcare. Available online: https:\/\/justnebulizers.com\/products\/smart-mesh-nebulizer-by-briutcare."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Moon, S.-H., Chang, K.H., Park, H.M., Park, B.J., Yoo, S.K., and Nam, K.C. (2021). Effects of Driving Frequency and Voltage on the Performances of Vibrating Mesh Nebulizers. Appl. Sci., 11.","DOI":"10.3390\/app11031296"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.optom.2018.12.003","article-title":"Advances in diagnostic applications for monitoring intraocular pressure in Glaucoma: A review","volume":"12","author":"Sanchez","year":"2019","journal-title":"J. Optom."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"806","DOI":"10.4187\/respcare.03554","article-title":"Aerosolized Medications for Gene and Peptide Therapy","volume":"60","author":"Laube","year":"2015","journal-title":"Respir. Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1183\/09031936.01.00220001","article-title":"European Respiratory Society Guidelines on the use of nebulizers: Guidelines prepared by a European Respiratory Society Task Force on the use of nebulizers","volume":"18","author":"Boe","year":"2001","journal-title":"Eur. Respir. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.2147\/IJN.S162306","article-title":"Montmorillonite\/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma","volume":"13","author":"Li","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"119961","DOI":"10.1016\/j.biomaterials.2020.119961","article-title":"Dually functional hollow ceria nanoparticle platform for intraocular drug delivery: A push beyond the limits of static and dynamic ocular barriers toward glaucoma therapy","volume":"243","author":"Luo","year":"2020","journal-title":"Biomaterials"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5915","DOI":"10.2147\/IJN.S382968","article-title":"Critical Evaluation of Multifunctional Betaxolol Hydrochloride Nanoformulations for Effective Sustained Intraocular Pressure Reduction","volume":"17","author":"Hu","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e08236","DOI":"10.1002\/smll.202508236","article-title":"Filomicelle-Embedded Composite Hydrogels for Localized Gelation within the Anterior Chamber of the Eye","volume":"22","author":"Kim","year":"2026","journal-title":"Small"},{"key":"ref_42","first-page":"100847","article-title":"Contact lens as an emerging platform for ophthalmic drug delivery: A systematic review","volume":"18","author":"Yang","year":"2023","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1089\/jamp.2024.29110.jbf","article-title":"Nebulizers","volume":"37","author":"Fink","year":"2024","journal-title":"J. Aerosol Med. Pulm. Drug Deliv."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kowsigan, M., Shetty, R., and Vyas, A. (2023, January 24\u201326). An Enhanced Smart Nebulizer Using IoT in the Treatment of Asthma Patients. Proceedings of the 2023 Innovations in Power and Advanced Computing Technologies (i-PACT), Kuala Lumpur, Malaysia.","DOI":"10.1109\/i-PACT58649.2023.10434785"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/4\/404\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:09:22Z","timestamp":1775563762000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/4\/404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,25]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["pharmaceutics18040404"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18040404","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,25]]}}}