{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T01:58:04Z","timestamp":1782871084004,"version":"3.54.5"},"reference-count":67,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Acibadem University Scientific Research Projects Coordination Unit","award":["THD-2024-2211"],"award-info":[{"award-number":["THD-2024-2211"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Brimonidine tartrate (BRT), a selective \u03b12-adrenergic receptor agonist, is commonly used in the treatment of glaucoma. However, conventional eye drop formulations suffer from poor ocular bioavailability and rapid elimination. This study aimed to develop and evaluate BRT-loaded ethosomes as a nanocarrier-based alternative to enhance intraocular delivery and therapeutic efficacy. Methods: Ethosomes were prepared using the thin-film hydration method and optimized via central composite design. The optimized formulation was subjected to physicochemical characterization, in vitro release testing, and ocular irritation assessment using the Hen egg test\u2014chorioallantoic membrane (HET-CAM) model. Additionally, the intraocular pressure (IOP)-lowering efficacy of the formulation was evaluated in a rat glaucoma model. Results: The optimized ethosomal formulation exhibited favorable physicochemical properties, including a mean particle size of 122.6 \u00b1 0.7 nm, zeta potential of \u22121.8 \u00b1 0.9 mV, and encapsulation efficiency of 87.33 \u00b1 0.04%. In vitro release data followed Higuchi kinetics. HET-CAM analysis indicated non-irritancy. In vivo, the ethosomal BRT formulation achieved comparable IOP-lowering effects to the marketed eye drops at one-third of the dose. Conclusions: The developed BRT-loaded ethosomal system demonstrated promising physicochemical stability, sustained release, and therapeutic potential. These findings suggest that ethosomes may offer a safe and effective strategy for enhancing the ocular delivery of BRT in glaucoma therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics18020210","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:05:47Z","timestamp":1770372347000},"page":"210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development of Brimonidine-Loaded Ethosomes for Glaucoma: Investigation of Intraocular Pressure-Lowering Potential In Vivo"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6212-2706","authenticated-orcid":false,"given":"Samet","family":"\u00d6zdemir","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul Health and Technology University, Istanbul 34445, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6960-6364","authenticated-orcid":false,"given":"Ali Asram","family":"Sa\u011f\u0131ro\u011flu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University-Cerrahpasa, Istanbul 34500, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3535-4915","authenticated-orcid":false,"given":"Eslim","family":"\u015een","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University-Cerrahpasa, Istanbul 34500, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4224-7453","authenticated-orcid":false,"given":"B\u00fc\u015fra","family":"Gelmez Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University-Cerrahpasa, Istanbul 34500, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laman","family":"Karimli","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul 34636, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5724-9809","authenticated-orcid":false,"given":"Meltem Ezgi","family":"Durgun K\u0131l\u0131\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul Health and Technology University, Istanbul 34445, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Riza Cenk","family":"Celebi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Istanbul Health and Technology University, Istanbul 34445, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9110-3704","authenticated-orcid":false,"given":"Y\u0131ld\u0131z","family":"\u00d6zsoy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1007\/s00401-016-1609-2","article-title":"Glaucoma: The retina and beyond","volume":"132","author":"Davis","year":"2016","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.3390\/encyclopedia2040124","article-title":"Pathogenesis of Glaucoma","volume":"2","author":"Macanian","year":"2022","journal-title":"Encyclopedia"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/ceo.13989","article-title":"Medical therapy for glaucoma: A review","volume":"50","author":"Casson","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1001\/archopht.1995.01100120044006","article-title":"Effects of brimonidine on aqueous humor dynamics in human eyes","volume":"113","author":"Toris","year":"1995","journal-title":"Arch. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1124\/jpet.119.256933","article-title":"Ocular Drug Delivery: Present Innovations and Future Challenges","volume":"370","author":"Gote","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Giri, B.R., Jakka, D., Sandoval, M.A., Kulkarni, V.R., and Bao, Q. (2024). Advancements in Ocular Therapy: A Review of Emerging Drug Delivery Approaches and Pharmaceutical Technologies. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16101325"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s12951-023-01992-2","article-title":"Nanotechnology-based ocular drug delivery systems: Recent advances and future prospects","volume":"21","author":"Li","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"124741","DOI":"10.1016\/j.ijpharm.2024.124741","article-title":"A one-platform comparison study of brinzolamide-loaded liposomes, niosomes, transfersomes, and transniosomes for better management of glaucoma","volume":"666","author":"Srivastava","year":"2024","journal-title":"Int. J. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Batur, E., Ozdemir, S., Durgun, M.E., and Ozsoy, Y. (2024). Vesicular Drug Delivery Systems: Promising Approaches in Ocular Drug Delivery. Pharmaceuticals, 17.","DOI":"10.3390\/ph17040511"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"123021","DOI":"10.1016\/j.ijpharm.2023.123021","article-title":"Timolol-loaded ethosomes for ophthalmic delivery: Reduction of high intraocular pressure in vivo","volume":"640","author":"Uner","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ahmed, T.A., Alzahrani, M.M., Sirwi, A., and Alhakamy, N.A. (2021). Study the Antifungal and Ocular Permeation of Ketoconazole from Ophthalmic Formulations Containing Trans-Ethosomes Nanoparticles. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13020151"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2200331","DOI":"10.1002\/adtp.202200331","article-title":"Ethosomal Nanoformulations for Combinational Photothermal Therapy of Fungal Keratitis","volume":"6","author":"Sushma","year":"2023","journal-title":"Adv. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5837","DOI":"10.2147\/IJN.S86186","article-title":"Development, characterization, and skin delivery studies of related ultradeformable vesicles: Transfersomes, ethosomes, and transethosomes","volume":"10","author":"Ascenso","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4869","DOI":"10.2147\/IJN.S140835","article-title":"Design, optimization and characterization of coenzyme Q10- and D-panthenyl triacetate-loaded liposomes","volume":"12","author":"Celik","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Alam, P., Shakeel, F., Foudah, A.I., Alshehri, S., Salfi, R., Alqarni, M.H., and Aljarba, T.M. (2022). Central Composite Design (CCD) for the Optimisation of Ethosomal Gel Formulation of Punica granatum Extract: In Vitro and In Vivo Evaluations. Gels, 8.","DOI":"10.3390\/gels8080511"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ismail, T.A., Shehata, T.M., Mohamed, D.I., Elsewedy, H.S., and Soliman, W.E. (2021). Quality by Design for Development, Optimization and Characterization of Brucine Ethosomal Gel for Skin Cancer Delivery. Molecules, 26.","DOI":"10.3390\/molecules26113454"},{"key":"ref_17","unstructured":"Guideline, I. (2022). Validation of Analytical Procedures Q2 (R2), ICH."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1080\/10837450.2020.1860087","article-title":"An evaluation of tocotrienol ethosomes for transdermal delivery using Strat-M\u00ae membrane and excised human skin","volume":"26","author":"Nair","year":"2021","journal-title":"Pharm. Dev. Technol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0168-3659(94)00085-9","article-title":"Zero-order release from biphasic polymer hydrogels","volume":"34","author":"Varelas","year":"1995","journal-title":"J. Control. Release"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.ejpb.2015.02.017","article-title":"Release kinetics of paclitaxel and cisplatin from two and three layered gold nanoparticles","volume":"92","author":"England","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1002\/jps.2600501018","article-title":"Rate of release of medicaments from ointment bases containing drugs in suspension","volume":"50","author":"Higuchi","year":"1961","journal-title":"J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1021\/ie50260a018","article-title":"Dependence of Reaction Velocity upon surface and Agitation","volume":"23","author":"Hixson","year":"1931","journal-title":"Ind. Eng. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/S0002-9394(01)00834-0","article-title":"Brimonidine 0.2% given two or three times daily versus timolol maleate 0.5% in primary open-angle glaucoma","volume":"131","author":"Konstas","year":"2001","journal-title":"Am. J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0002-9394(00)00381-0","article-title":"Brimonidine 0.2% versus dorzolamide 2% each given three times daily to reduce intraocular pressure","volume":"129","author":"Stewart","year":"2000","journal-title":"Am. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1097\/00061198-200404000-00015","article-title":"Comparison of the Safety and Efficacy of Dorzolamide 2% and Brimonidine 0.2% in Patients with Glaucoma or Ocular Hypertension","volume":"13","author":"Whitson","year":"2004","journal-title":"J. Glaucoma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1001\/archopht.124.9.1230","article-title":"Twice-Daily 0.2% Brimonidine\u20130.5% Timolol Fixed-Combination Therapy vs Monotherapy With Timolol or Brimonidine in Patients With Glaucoma or Ocular Hypertension: A 12-Month Randomized Trial","volume":"124","author":"Sherwood","year":"2006","journal-title":"Arch. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/00061198-200204000-00007","article-title":"Twelve-Month Evaluation of Brimonidine-Purite Versus Brimonidine in Patients With Glaucoma or Ocular Hypertension","volume":"11","author":"Katz","year":"2002","journal-title":"J. Glaucoma"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1208\/s12249-011-9643-9","article-title":"Nanovesicular formulation of brimonidine tartrate for the management of glaucoma: In vitro and in vivo evaluation","volume":"12","author":"Maiti","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2753","DOI":"10.2147\/IJN.S370192","article-title":"Augmented in vitro and in vivo Profiles of Brimonidine Tartrate Using Gelatinized-Core Liposomes","volume":"17","author":"Elkheshen","year":"2022","journal-title":"Int. J. Nanomed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jddst.2019.04.036","article-title":"Formulation and evaluation of cubosomes drug delivery system for treatment of glaucoma: Ex-vivo permeation and in-vivo pharmacodynamic study","volume":"52","author":"Eldeeb","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125111","DOI":"10.1016\/j.molliq.2024.125111","article-title":"Development and characterization of topical ethosomal gel for improved antifungal therapeutics","volume":"405","author":"Gupta","year":"2024","journal-title":"J. Mol. Liq."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1208\/s12249-025-03159-8","article-title":"Nanovesicular Drug Delivery Systems for Rare Ocular Diseases: Advances, Challenges, and Future Directions","volume":"26","author":"Sultana","year":"2025","journal-title":"AAPS PharmSciTech"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12951-021-00833-4","article-title":"Central composite design for the development of carvedilol-loaded transdermal ethosomal hydrogel for extended and enhanced anti-hypertensive effect","volume":"19","author":"Amarachinta","year":"2021","journal-title":"J. Nanobiotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mohapatra, S., Mirza, M.A., Ahmad, S., Farooq, U., Ansari, M.J., Kohli, K., and Iqbal, Z. (2023). Quality by Design Assisted Optimization and Risk Assessment of Black Cohosh Loaded Ethosomal Gel for Menopause: Investigating Different Formulation and Process Variables. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020465"},{"key":"ref_35","first-page":"627","article-title":"Characterization of paracellular and aqueous penetration routes in cornea, conjunctiva, and sclera","volume":"38","author":"Kananen","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Hansen, M.E., Ibrahim, Y., Desai, T.A., and Koval, M. (2024). Nanostructure-Mediated Transport of Therapeutics through Epithelial Barriers. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137098"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Natsheh, H., and Touitou, E. (2020). Phospholipid Vesicles for Dermal\/Transdermal and Nasal Administration of Active Molecules: The Effect of Surfactants and Alcohols on the Fluidity of Their Lipid Bilayers and Penetration Enhancement Properties. Molecules, 25.","DOI":"10.3390\/molecules25132959"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.jddst.2019.05.048","article-title":"Formulation development of ethosomes containing indomethacin for transdermal delivery","volume":"52","author":"Sakdiset","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1002\/anie.199416851","article-title":"Sterically Stabilized Vesicles","volume":"33","author":"Lasic","year":"1994","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0005-2736(91)90162-2","article-title":"Sterically stabilized liposomes: A hypothesis on the molecular origin of the extended circulation times","volume":"1070","author":"Lasic","year":"1991","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_41","unstructured":"Lasic, D.D. (1993). Liposomes: From Physics to Applications, Elsevier."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1080\/10717544.2019.1609622","article-title":"Proniosomal gel-derived niosomes: An approach to sustain and improve the ocular delivery of brimonidine tartrate; formulation, in-vitro characterization, and in-vivo pharmacodynamic study","volume":"26","author":"Salah","year":"2019","journal-title":"Drug Deliv."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Nijhawan, H.P., Vyas, J., Verma, P., and Yadav, K.S. (2025). Hyaluronic acid-coated cubosomal in situ gel for Brimonidine Tartrate: A sustained delivery system with enhanced ocular bioavailability and intraocular pressure reduction. J. Biomater. Sci. Polym. Ed., 1\u201334.","DOI":"10.1080\/09205063.2025.2543071"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s40199-023-00500-z","article-title":"Development of brimonidine niosomes laden contact lenses for extended release and promising delivery system in glaucoma treatment","volume":"32","author":"Tripathi","year":"2024","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e202400090","DOI":"10.1002\/nano.202400090","article-title":"Bortezomib (BOR)-Pegylated-Gold Nanovector: Synthesis, Spectroscopic Evaluation and Diagnostic Tool as Galectin-1 Biomarker","volume":"6","author":"Khan","year":"2025","journal-title":"Nano Sel."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.bbamem.2016.12.005","article-title":"Characterization of extracellular vesicles by IR spectroscopy: Fast and simple classification based on amide and CH stretching vibrations","volume":"1859","author":"Varga","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_47","unstructured":"Silverstein, R.M., Webster, F.X., Kiemle, D.J., and Bryce, D.L. (2014). Spectrometric Identification of Organic Compounds, Wiley."},{"key":"ref_48","first-page":"e68280","article-title":"Ex Vivo Irritation Evaluation of a Novel Brimonidine Nanoemulsion Using the Hen\u2019s Egg Test on Chorioallantoic Membrane (HET-CAM)","volume":"16","author":"Smail","year":"2024","journal-title":"Cureus"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"416","DOI":"10.35333\/jrp.2020.164","article-title":"Development and evaluation of a pH triggered in situ ocular gel of brimonidine tartrate","volume":"24","author":"Bharath","year":"2020","journal-title":"J. Res. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1517\/17425255.2013.783013","article-title":"Alternative methods for ocular toxicology testing: Validation, applications and troubleshooting","volume":"9","author":"Dholakiya","year":"2013","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.yrtph.2011.02.003","article-title":"Eye irritation potential: Usefulness of the HET-CAM under the Globally Harmonized System of classification and labeling of chemicals (GHS)","volume":"59","author":"Scheel","year":"2011","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ijpharm.2004.10.026","article-title":"Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system","volume":"290","author":"Aggarwal","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1208\/s12249-011-9675-1","article-title":"Brimonidine tartrate-eudragit long-acting nanoparticles: Formulation, optimization, in vitro and in vivo evaluation","volume":"12","author":"Bhagav","year":"2011","journal-title":"AAPS PharmSciTech"},{"key":"ref_54","first-page":"594","article-title":"Chitosan nanoparticles for controlled delivery of brimonidine tartrate to the ocular membrane","volume":"66","author":"Singh","year":"2011","journal-title":"Pharmazie"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1167\/tvst.4.3.12","article-title":"Natural Bioadhesive Biodegradable Nanoparticle-Based Topical Ophthalmic Formulations for Management of Glaucoma","volume":"4","author":"Ibrahim","year":"2015","journal-title":"Transl. Vis. Sci. Technol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"8639","DOI":"10.1038\/s41598-017-09379-8","article-title":"Long Term Glaucoma Drug Delivery Using a Topically Retained Gel\/Microsphere Eye Drop","volume":"7","author":"Fedorchak","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1080\/02652048.2018.1425753","article-title":"Nanostructured lipid carriers for intraocular brimonidine localisation: Development, in-vitro and in-vivo evaluation","volume":"35","author":"Farid","year":"2018","journal-title":"J. Microencapsul."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1080\/02713683.2021.1942071","article-title":"Phase Transition Microemulsion of Brimonidine Tartrate for Glaucoma Therapy: Preparation, Characterization and Pharmacodynamic Study","volume":"46","author":"Gautam","year":"2021","journal-title":"Curr. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1080\/02713683.2021.1916037","article-title":"Optimization and Characterization of Brimonidine Tartrate Nanoparticles-loaded In Situ Gel for the Treatment of Glaucoma","volume":"46","author":"Sharma","year":"2021","journal-title":"Curr. Eye Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9445","DOI":"10.1021\/acsami.0c18626","article-title":"Improved Treatment Options for Glaucoma with Brimonidine-Loaded Lipid DNA Nanoparticles","volume":"13","author":"Schnichels","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"103594","DOI":"10.1016\/j.jddst.2022.103594","article-title":"Ophthalmic suspension of Brimonidine for sustained delivery using nano-resin\/drug complex technique","volume":"75","author":"Khopade","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"356","DOI":"10.4103\/0975-1483.71623","article-title":"Preparation and Evaluation of Nano-vesicles of Brimonidine Tartrate as an Ocular Drug Delivery System","volume":"2","author":"Prabhu","year":"2010","journal-title":"J. Young Pharm."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Gonzalez-Cela-Casamayor, M.A., Lopez-Cano, J.J., Bravo-Osuna, I., Andres-Guerrero, V., Vicario-de-la-Torre, M., Guzman-Navarro, M., Benitez-Del-Castillo, J.M., Herrero-Vanrell, R., and Molina-Martinez, I.T. (2022). Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14071405"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"374","DOI":"10.4103\/0110-5558.76435","article-title":"Niosome: A future of targeted drug delivery systems","volume":"1","author":"Kazi","year":"2010","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7372306","DOI":"10.1155\/2016\/7372306","article-title":"Niosomes as Nanoparticular Drug Carriers: Fundamentals and Recent Applications","volume":"2016","author":"Seleci","year":"2016","journal-title":"J. Nanomater."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"192","DOI":"10.2174\/1567201811666140723115852","article-title":"Stability studies on piroxicam encapsulated niosomes","volume":"12","author":"Ertekin","year":"2015","journal-title":"Curr. Drug Deliv."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s40204-021-00164-5","article-title":"Evaluation of sonication on stability-indicating properties of optimized pilocarpine hydrochloride-loaded niosomes in ocular drug delivery","volume":"10","author":"Ilomuanya","year":"2021","journal-title":"Prog. Biomater."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/2\/210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T10:13:20Z","timestamp":1770372800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/2\/210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":67,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["pharmaceutics18020210"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18020210","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}