{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:50:45Z","timestamp":1791607845829,"version":"4.3.4"},"reference-count":87,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"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>Spaceflight-associated dry eye syndrome (SADES) has been reported among astronauts during both International Space Station (ISS) and Space Transportation System (STS) missions. As future missions extend beyond low Earth orbit, the physiological challenges of spaceflight include microgravity, radiation, and environmental stressors, which may further exacerbate the development of ocular surface disease. A deeper understanding of the underlying pathophysiology, along with the exploration of innovative countermeasures, is critical. In this review, we examine nanomedicine as a promising countermeasure for managing ophthalmic conditions in space, with the goal of enhancing visual health and mission readiness for long-duration exploration-class missions.<\/jats:p>","DOI":"10.3390\/pharmaceutics17070847","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T06:46:12Z","timestamp":1751438772000},"page":"847","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tear Film and Keratitis in Space: Fluid Dynamics and Nanomedicine Strategies for Ocular Protection in Microgravity"],"prefix":"10.3390","volume":"17","author":[{"given":"Ryung","family":"Lee","sequence":"first","affiliation":[{"name":"The Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8574-2895","authenticated-orcid":false,"given":"Rahul","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3088-7543","authenticated-orcid":false,"given":"Jainam","family":"Shah","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-827X","authenticated-orcid":false,"given":"Joshua","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Michigan Kellogg Eye Center, Ann Arbor, MI 48105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan","family":"Waisberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 1TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9460-1269","authenticated-orcid":false,"given":"Alireza","family":"Tavakkoli","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Engineering, University of Reno, Reno, NV 89512, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S203","DOI":"10.1016\/S0039-6257(00)00203-4","article-title":"The Ocular Surface and Tear Film and Their Dysfunction in Dry Eye Disease","volume":"45","author":"Rolando","year":"2001","journal-title":"Surv. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1080\/02713683.2022.2162088","article-title":"Association of Tear Cytokine Concentrations with Symptoms and Signs of Dry Eye Disease: Baseline Data from the Dry Eye Assessment and Management (DREAM) Study","volume":"48","author":"Roy","year":"2023","journal-title":"Curr. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1152\/jappl.1996.81.1.408","article-title":"Central Venous Pressure in Humans during Microgravity","volume":"81","author":"Foldager","year":"1996","journal-title":"J. Appl. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.cell.2020.10.050","article-title":"Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration","volume":"183","author":"Afshinnekoo","year":"2020","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41526-020-0097-9","article-title":"Spaceflight Associated Neuro-Ocular Syndrome (SANS) and the Neuro-Ophthalmologic Effects of Microgravity: A Review and an Update","volume":"6","author":"Lee","year":"2020","journal-title":"npj Microgravity"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1038\/s41433-024-03204-z","article-title":"Corneal Wound Healing in Spaceflight: Implications of Microgravity-Induced Molecular Signaling Modulations for Corneal Health","volume":"38","author":"Lee","year":"2024","journal-title":"Eye"},{"key":"ref_7","first-page":"151","article-title":"Molecular and Biomechanical Changes of the Cornea and Lens in Spaceflight","volume":"45","author":"Panzo","year":"2025","journal-title":"Life Sci. Space Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41526-020-0104-1","article-title":"How Does Spaceflight Affect the Acquired Immune System?","volume":"6","author":"Akiyama","year":"2020","journal-title":"npj Microgravity"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Lee, R., Ong, J., Waisberg, E., Mader, T., Berdahl, J., Suh, A., Panzo, N., Memon, H., Sampige, R., and Katsev, B. (2025). Potential Risks of Ocular Molecular and Cellular Changes in Spaceflight. Semin. Ophthalmol., 1\u201311.","DOI":"10.1080\/08820538.2025.2471443"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"855791","DOI":"10.3389\/fbioe.2022.855791","article-title":"Medical Image-Based Computational Fluid Dynamics and Fluid-Structure Interaction Analysis in Vascular Diseases","volume":"10","author":"He","year":"2022","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"SA491","DOI":"10.1088\/0953-8984\/2\/S\/078","article-title":"Fluid Statics and Dynamics in Microgravity","volume":"2","author":"Langbein","year":"1990","journal-title":"J. Phys. Condens. Matter"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/imammb\/dqu001","article-title":"Modelling the Evaporation of a Tear Film over a Contact Lens","volume":"32","author":"Talbott","year":"2015","journal-title":"Math. Med. Biol. A J. IMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3109\/02713688909000031","article-title":"Tear Film Stability and Tear Surface Tension","volume":"8","author":"Tiffany","year":"1989","journal-title":"Curr. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1076\/ceyr.17.11.1058.5233","article-title":"In Vivo Tear-Film Thickness Determination and Implications for Tear-Film Stability","volume":"17","author":"Creech","year":"1998","journal-title":"Curr. Eye Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1006\/jcis.1996.0595","article-title":"Deposition and Thinning of the Human Tear Film","volume":"184","author":"Wong","year":"1996","journal-title":"J. Colloid Interface Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.bpj.2021.12.033","article-title":"Biophysical Properties of Tear Film Lipid Layer I. Surface Tension and Surface Rheology","volume":"121","author":"Xu","year":"2022","journal-title":"Biophys. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S0002-9394(14)71692-7","article-title":"Gravity, Blink Rate, and Lacrimal Drainage Capacity","volume":"124","author":"Sahlin","year":"1997","journal-title":"Am. J. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/00004397-197301310-00009","article-title":"The Dynamics and Drainage of Tears","volume":"13","author":"Maurice","year":"1973","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_19","first-page":"75","article-title":"Spaceflight Associated Dry Eye Syndrome (SADES): Radiation, Stressors, and Ocular Surface Health","volume":"43","author":"Lee","year":"2024","journal-title":"Life Sci. Space Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/s41526-024-00446-9","article-title":"Challenges for the Human Immune System after Leaving Earth","volume":"10","author":"Marchal","year":"2024","journal-title":"npj Microgravity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"383","DOI":"10.2147\/IJGM.S114188","article-title":"Incidence of Clinical Symptoms during Long-Duration Orbital Spaceflight","volume":"9","author":"Crucian","year":"2016","journal-title":"Int. J. Gen. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4954","DOI":"10.1038\/s41467-024-49211-2","article-title":"Single-Cell Multi-Ome and Immune Profiles of the Inspiration4 Crew Reveal Conserved, Cell-Type, and Sex-Specific Responses to Spaceflight","volume":"15","author":"Kim","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41526-017-0015-y","article-title":"Latent Virus Reactivation in Astronauts on the International Space Station","volume":"3","author":"Mehta","year":"2017","journal-title":"NPJ Microgravity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.trsl.2021.05.005","article-title":"Immune Responses to Injury and Their Links to Eye Disease","volume":"236","author":"Stepp","year":"2021","journal-title":"Transl. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1002\/cpt.2432","article-title":"Clinical and Molecular Perspectives on Inflammation-Mediated Regulation of Drug Metabolism and Transport","volume":"112","author":"Dunvald","year":"2022","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0002-9394(01)01365-4","article-title":"Impaired Functional Visual Acuity of Dry Eye Patients","volume":"133","author":"Goto","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Shah, J., Ong, J., Lee, R., Suh, A., Waisberg, E., Gibson, C.R., Berdahl, J., and Mader, T.H. (2025). Risk of Permanent Corneal Injury in Microgravity: Spaceflight-Associated Hazards, Challenges to Vision Restoration, and Role of Biotechnology in Long-Term Planetary Missions. Life, 15.","DOI":"10.3390\/life15040602"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Barratt, M.R., Baker, E.S., and Pool, S.L. (2019). Principles of Clinical Medicine for Space Flight, Springer New York.","DOI":"10.1007\/978-1-4939-9889-0"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Crucian, B.E., Chouk\u00e8r, A., Simpson, R.J., Mehta, S., Marshall, G., Smith, S.M., Zwart, S.R., Heer, M., Ponomarev, S., and Whitmire, A. (2018). Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01437"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1002\/jmv.21173","article-title":"Asymptomatic Reactivation and Shed of Infectious Varicella Zoster Virus in Astronauts","volume":"80","author":"Cohrs","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rooney, B.V., Crucian, B.E., Pierson, D.L., Laudenslager, M.L., and Mehta, S.K. (2019). Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00016"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1007\/s40588-023-00202-9","article-title":"Intimate Relationship Between Stress and Human Alpha-Herpes Virus 1 (HSV-1) Reactivation from Latency","volume":"10","author":"Jones","year":"2023","journal-title":"Curr. Clin. Microbiol. Rep."},{"key":"ref_33","first-page":"917","article-title":"The Clinical Features of Viral Keratitis and a Concept of Their Pathogenesis","volume":"51","author":"Jones","year":"1958","journal-title":"Proc. R. Soc. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/NHH.0000000000000791","article-title":"Herpes Simplex Virus Keratitis","volume":"37","author":"Harris","year":"2019","journal-title":"Home Healthc. Now."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1089\/ast.2021.0009","article-title":"Spaceflight Virology: What Do We Know about Viral Threats in the Spaceflight Environment?","volume":"22","author":"Runzheimer","year":"2022","journal-title":"Astrobiology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hatami, H., Ghaffari Jolfayi, A., Ebrahimi, A., Golmohammadi, S., Zangiabadian, M., and Nasiri, M.J. (2021). Contact Lens Associated Bacterial Keratitis: Common Organisms, Antibiotic Therapy, and Global Resistance Trends: A Systematic Review. Front. Ophthalmol., 1.","DOI":"10.3389\/fopht.2021.759271"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1016\/S0142-9612(01)00161-2","article-title":"Bacterial Interactions with Contact Lenses; Effects of Lens Material, Lens Wear and Microbial Physiology","volume":"22","author":"Willcox","year":"2001","journal-title":"Biomaterials"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2147\/IDR.S67275","article-title":"Impact of Space Flight on Bacterial Virulence and Antibiotic Susceptibility","volume":"8","author":"Taylor","year":"2015","journal-title":"IDR"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5136","DOI":"10.1167\/iovs.10-7048","article-title":"Inflammation and the Nervous System: The Connection in the Cornea in Patients with Infectious Keratitis","volume":"52","author":"Cruzat","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","first-page":"75","article-title":"Spaceflight Associated Dry Eye Syndrome (SADES): Outflow Biophysics and Infection Risk","volume":"43","author":"Lee","year":"2025","journal-title":"J. Space Saf. Eng."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Marra, D., Ferraro, R., and Caserta, S. (2024). Biofilm Contamination in Confined Space Stations: Reduction, Coexistence or an Opportunity?. Front. Mater., 11.","DOI":"10.3389\/fmats.2024.1374666"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Flores, P., Luo, J., Mueller, D.W., Muecklich, F., and Zea, L. (2024). Space Biofilms\u2014An Overview of the Morphology of Pseudomonas Aeruginosa Biofilms Grown on Silicone and Cellulose Membranes on Board the International Space Station. Biofilm, 7.","DOI":"10.1016\/j.bioflm.2024.100182"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41526-021-00136-w","article-title":"Evaluating the Effect of Spaceflight on the Host\u2013Pathogen Interaction between Human Intestinal Epithelial Cells and Salmonella Typhimurium","volume":"7","author":"Barrila","year":"2021","journal-title":"NPJ Microgravity"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/s41579-019-0186-5","article-title":"Bacterial Quorum Sensing in Complex and Dynamically Changing Environments","volume":"17","author":"Mukherjee","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e01124-13","DOI":"10.1128\/genomeA.01124-13","article-title":"Genome Sequence of Pseudomonas Aeruginosa Strain LCT-PA41, with Changed Metabolism after Space Flight","volume":"2","author":"Liu","year":"2014","journal-title":"Genome Announc."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Morrison, M.D., Thissen, J.B., Karouia, F., Mehta, S., Urbaniak, C., Venkateswaran, K., Smith, D.J., and Jaing, C. (2021). Investigation of Spaceflight Induced Changes to Astronaut Microbiomes. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.659179"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Bharindwal, S., Goswami, N., Jha, P., Pandey, S., and Jobby, R. (2023). Prospective Use of Probiotics to Maintain Astronaut Health during Spaceflight. Life, 13.","DOI":"10.3390\/life13030727"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1097\/ICO.0b013e318191695b","article-title":"Fungal Keratitis: Changing Pathogens and Risk Factors","volume":"28","author":"Jurkunas","year":"2009","journal-title":"Cornea"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1093\/mmy\/myv121","article-title":"Comprehensive Analysis of the Skin Fungal Microbiota of Astronauts during a Half-Year Stay at the International Space Station","volume":"54","author":"Sugita","year":"2016","journal-title":"Med. Mycol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Checinska Sielaff, A., Urbaniak, C., Mohan, G.B.M., Stepanov, V.G., Tran, Q., Wood, J.M., Minich, J., McDonald, D., Mayer, T., and Knight, R. (2019). Characterization of the Total and Viable Bacterial and Fungal Communities Associated with the International Space Station Surfaces. Microbiome, 7.","DOI":"10.1186\/s40168-019-0666-x"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100007","DOI":"10.1016\/j.jahd.2024.100007","article-title":"Allergy and Hypersensitivity Diseases in Space: Physiological Changes, Clinical Aspects, and Mechanisms with Countermeasures","volume":"2","author":"Godard","year":"2024","journal-title":"J. Allergy Hypersensitivity Dis."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Crabb\u00e9, A., Nielsen-Preiss, S.M., Woolley, C.M., Barrila, J., Buchanan, K., McCracken, J., Inglis, D.O., Searles, S.C., Nelman-Gonzalez, M.A., and Ott, C.M. (2013). Spaceflight Enhances Cell Aggregation and Random Budding in Candida Albicans. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080677"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e00570-20","DOI":"10.1128\/MRA.00570-20","article-title":"Draft Genome Sequences of Rhodotorula Mucilaginosa Strains Isolated from the International Space Station","volume":"9","author":"Daudu","year":"2020","journal-title":"Microbiol. Resour. Announc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1111\/1758-2229.13078","article-title":"Melanin Protects Cryptococcus Neoformans from Spaceflight Effects","volume":"14","author":"Cordero","year":"2022","journal-title":"Env. Microbiol. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jid.2019.09.010","article-title":"Redox Activities of Melanins Investigated by Electrochemical Reverse Engineering: Implications for Their Roles in Oxidative Stress","volume":"140","author":"Kim","year":"2020","journal-title":"J. Investig. Dermatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.ajo.2007.02.016","article-title":"Clinical Characteristics and Outcome of Candida Keratitis","volume":"143","author":"Sun","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.2147\/OPTH.S7953","article-title":"Candida Albicans Keratitis in an Immunocompromised Patient","volume":"4","author":"Hassan","year":"2010","journal-title":"Clin. Ophthalmol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5149","DOI":"10.1167\/iovs.18-24690","article-title":"Spontaneous Eye Blink Patterns in Dry Eye: Clinical Correlations","volume":"59","author":"Su","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1080\/21691401.2017.1349779","article-title":"Preparation and Evaluation of Novel Chitosan: Gelrite Ocular System Containing Besifloxacin for Topical Treatment of Bacterial Conjunctivitis: Scintigraphy, Ocular Irritation and Retention Assessment","volume":"46","author":"Ameeduzzafar","year":"2018","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2966","DOI":"10.1021\/acs.molpharmaceut.6b00182","article-title":"Novel Water-Soluble Mucoadhesive Carbosilane Dendrimers for Ocular Administration","volume":"13","author":"Ponchel","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1016\/j.xphs.2016.03.006","article-title":"\u03b1-Lipoic Acid in Soluplus(\u00ae) Polymeric Nanomicelles for Ocular Treatment of Diabetes-Associated Corneal Diseases","volume":"105","author":"Concheiro","year":"2016","journal-title":"J. Pharm. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1039\/b600913c","article-title":"Imparting Size, Shape, and Composition Control of Materials for Nanomedicine","volume":"35","author":"Euliss","year":"2006","journal-title":"Chem. Soc. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Abourehab, M.A.S., Pramanik, S., Abdelgawad, M.A., Abualsoud, B.M., Kadi, A., Ansari, M.J., and Deepak, A. (2022). Recent Advances of Chitosan Formulations in Biomedical Applications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810975"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/jphp.12104","article-title":"Dendrimers for Gene Delivery\u2014A Potential Approach for Ocular Therapy?","volume":"66","author":"Chaplot","year":"2014","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jconrel.2011.01.010","article-title":"Development and Characterization of Cyclosporine A Loaded Nanoparticles for Ocular Drug Delivery: Cellular Toxicity, Uptake, and Kinetic Studies","volume":"151","author":"Aksungur","year":"2011","journal-title":"J. Control Release"},{"key":"ref_66","first-page":"6011","article-title":"Formation of Ion Pairing as an Alternative to Improve Encapsulation an d Anticancer Activity of All-Trans Retinoic Acid Loaded in Solid Lipid Nanoparticles","volume":"7","author":"Carneiro","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2217\/17435889.2.1.11","article-title":"Ocular Drug Delivery: Nanomedicine Applications","volume":"2","author":"Vandervoort","year":"2007","journal-title":"Nanomedicine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1021\/acsami.2c18598","article-title":"Influence of the Size and Charge of Carbon Quantum Dots on Their Corneal Penetration and Permeation Enhancing Properties","volume":"15","author":"Barras","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"123048","DOI":"10.1016\/j.ijpharm.2023.123048","article-title":"Contact Lenses That Transform Gold into Nanoparticles for Prophylaxis of Light-Related Events and Photothermal Therapy","volume":"641","author":"Concheiro","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Ax, T., Ganse, B., Fries, F.N., Szentm\u00e1ry, N., de Paiva, C.S., March de Ribot, F., Jensen, S.O., Seitz, B., and Millar, T.J. (2023). Dry Eye Disease in Astronauts: A Narrative Review. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1281327"},{"key":"ref_71","first-page":"169","article-title":"The Ocular Surface during Spaceflight: Post-Mission Symptom Report, Extraterrestrial Risks, and in-Flight Therapeutics","volume":"46","author":"Ong","year":"2025","journal-title":"Life Sci. Space Res."},{"key":"ref_72","first-page":"53","article-title":"Biophysics of Ophthalmic Medications During Spaceflight: Principles of Ocular Fluid Dynamics and Pharmacokinetics in Microgravity","volume":"42","author":"Memon","year":"2024","journal-title":"Life Sci. Space Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.neubiorev.2020.05.007","article-title":"Countermeasures-Based Improvements in Stress, Immune System Dysregulation and Latent Herpesvirus Reactivation Onboard the International Space Station - Relevance for Deep Space Missions and Terrestrial Medicine","volume":"115","author":"Crucian","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1208\/s12249-009-9268-4","article-title":"Nanoemulsion as a Potential Ophthalmic Delivery System for Dorzolamide Hydrochloride","volume":"10","author":"Ammar","year":"2009","journal-title":"AAPS PharmSciTech"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1021\/bc5004313","article-title":"Functionalizing Liposomes with Anti-CD44 Aptamer for Selective Targeti Ng of Cancer Cells","volume":"26","author":"Alshaer","year":"2015","journal-title":"Bioconjugate Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2019.03.022","article-title":"A Novel FK506 Loaded Nanomicelles Consisting of Amino-Terminated Poly(Ethylene Glycol)-Block-Poly(D,L)-Lactic Acid and Hydroxypropyl Methylcellulose for Ocular Drug Delivery","volume":"562","author":"Liu","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"122740","DOI":"10.1016\/j.ijpharm.2023.122740","article-title":"Therapeutic Contact Lenses for the Treatment of Corneal and Ocular Surface Diseases: Advances in Extended and Targeted Drug Delivery","volume":"638","author":"Abdi","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.clae.2003.09.004","article-title":"Efficacy of Continuous Wear PureVision Contact Lenses for Therapeutic Use","volume":"27","author":"Arora","year":"2004","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1097\/ICO.0000000000000825","article-title":"Voriconazole-Loaded Nanostructured Lipid Carriers for Ocular Drug Delivery","volume":"35","author":"Andrade","year":"2016","journal-title":"Cornea"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41427-023-00478-9","article-title":"Development of Nanodrug-Based Eye Drops with Good Penetration Properties and ROS Responsiveness for Controllable Release to Treat Fungal Keratitis","volume":"15","author":"Niu","year":"2023","journal-title":"NPG Asia Mater."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1016\/j.ophtha.2011.06.021","article-title":"Optic Disc Edema, Globe Flattening, Choroidal Folds, and Hyperopic Shifts Observed in Astronauts after Long-Duration Space Flight","volume":"118","author":"Mader","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/WNO.0000000000000334","article-title":"Neuro-Ophthalmology of Space Flight","volume":"36","author":"Lee","year":"2016","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Kumar, R., Waisberg, E., Ong, J., Paladugu, P., Amiri, D., Saintyl, J., Yelamanchi, J., Nahouraii, R., Jagadeesan, R., and Tavakkoli, A. (2024). Artificial Intelligence-Based Methodologies for Early Diagnostic Precision and Personalized Therapeutic Strategies in Neuro-Ophthalmic and Neurodegenerative Pathologies. Brain Sci., 14.","DOI":"10.20944\/preprints202411.1672.v1"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1152\/jappl.1995.79.2.428","article-title":"Changes in Sympathoadrenal Response to Standing in Humans after Spaceflight","volume":"79","author":"Whitson","year":"1995","journal-title":"J. Appl. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"124098","DOI":"10.1016\/j.ijpharm.2024.124098","article-title":"Acetazolamide Encapsulation in Elastin like Recombinamers Using a Supercritical Antisolvent (SAS) Process for Glaucoma Treatment","volume":"657","author":"Vallejo","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.7150\/thno.23789","article-title":"Surface Impact on Nanoparticle-Based Magnetic Resonance Imaging Contrast Agents","volume":"8","author":"Zhang","year":"2018","journal-title":"Theranostics"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"125507","DOI":"10.1016\/j.ijpharm.2025.125507","article-title":"Acetazolamide-Loaded Intravitreal Implants for the Treatment of Glaucoma: Formulation, Physicochemical Characterization and Assessment of in Vitro and in Vivo Safety","volume":"674","author":"Ribeiro","year":"2025","journal-title":"Int. J. Pharm."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/847\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:00:49Z","timestamp":1760032849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/7\/847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,28]]},"references-count":87,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["pharmaceutics17070847"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17070847","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,28]]}}}