{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:45:33Z","timestamp":1788284733368,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,6]],"date-time":"2021-02-06T00:00:00Z","timestamp":1612569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Education and Ministry of Science and Technology","award":["MAT 2017-83858-C2-1-R"],"award-info":[{"award-number":["MAT 2017-83858-C2-1-R"]}]},{"name":"Thematic Research Network in Ophthalmology (Oftared) Carlos III National Institute of Health","award":["RD16\/0008\/0001, RD16\/0008\/0004, RD16\/0008\/0009"],"award-info":[{"award-number":["RD16\/0008\/0001, RD16\/0008\/0004, RD16\/0008\/0009"]}]},{"DOI":"10.13039\/501100002911","name":"Complutense University of Madrid","doi-asserted-by":"publisher","award":["UCM-920415"],"award-info":[{"award-number":["UCM-920415"]}],"id":[{"id":"10.13039\/501100002911","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CONACYT (Mexico)","award":["CONACYT"],"award-info":[{"award-number":["CONACYT"]}]},{"DOI":"10.13039\/501100014180","name":"Junta de Castilla y Le\u00f3n","doi-asserted-by":"publisher","award":["Junta de Castilla y Le\u00f3n"],"award-info":[{"award-number":["Junta de Castilla y Le\u00f3n"]}],"id":[{"id":"10.13039\/501100014180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Many diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres (Dx-MS) were prepared using the oil-in-water (O\/W) emulsion solvent evaporation technique. MS were characterized in terms of mean particle size and particle size distribution, external morphology, polymer integrity, drug content, and in vitro release profiles. MS were sterilized by gamma irradiation (25 kGy), and dexamethasone release profiles from sterilized and non-sterilized microspheres were compared by means of the similarity factor (f2). The mechanism of drug release before and after irradiation exposure of Dx-MS was identified using appropriate mathematical models. Dexamethasone release was sustained in vitro for 9 weeks. The evaluation of the in vivo tolerance was carried out in rabbit eyes, which received a sub-Tenon injection of 5 mg of sterilized Dx-MS (20\u201353 \u00b5m size containing 165.6 \u00b1 3.6 \u00b5g Dx\/mg MS) equivalent to 828 \u00b5g of Dx. No detectable increase in intraocular pressure was reported, and clinical and histological analysis of the ocular tissues showed no adverse events up to 6 weeks after the administration. According to the data presented in this work, the sub-Tenon administration of Dx-MS could be a promising alternative to successive intravitreal injections for the treatment of chronic diseases of the back of the eye.<\/jats:p>","DOI":"10.3390\/pharmaceutics13020228","type":"journal-article","created":{"date-parts":[[2021,2,14]],"date-time":"2021-02-14T08:53:56Z","timestamp":1613292836000},"page":"228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies"],"prefix":"10.3390","volume":"13","author":[{"given":"Deyanira","family":"Barbosa-Alfaro","sequence":"first","affiliation":[{"name":"Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), IdISSC, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0157-1932","authenticated-orcid":false,"given":"Vanessa","family":"Andr\u00e9s-Guerrero","sequence":"additional","affiliation":[{"name":"Innovation, Therapy and Pharmaceutical Development in Ophthalmology (InnOftal) Research Group, UCM 920415, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid (UCM), IdISSC, 28040 Madrid, Spain"},{"name":"Thematic Research Network in Ophthalmology (Oftared) Carlos III National Institute of Health, 28040 Madrid, 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of Presbyopia and Vision Impairment from Uncorrected Presbyopia: Systematic Review, Meta-analysis, and Modelling","volume":"125","author":"Fricke","year":"2018","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e888","DOI":"10.1016\/S2214-109X(17)30293-0","article-title":"Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: A systematic review and meta-analysis","volume":"5","author":"Bourne","year":"2017","journal-title":"Lancet Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1007\/s13346-016-0336-5","article-title":"Pharmaceutical microscale and nanoscale approaches for efficient treatment of ocular diseases","volume":"6","author":"Abal","year":"2016","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S1773-2247(13)50016-5","article-title":"Nano and microtechnologies for ophthalmic administration, an overview","volume":"23","year":"2013","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"683","DOI":"10.18433\/J3H60P","article-title":"Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses","volume":"18","author":"Ribeiro","year":"2015","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1016\/j.drudis.2019.05.031","article-title":"Recent advances in intraocular sustained-release drug delivery devices","volume":"24","author":"Cao","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1016\/S0142-9612(01)00291-5","article-title":"Dexamethasone\/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices","volume":"23","author":"Hickey","year":"2002","journal-title":"Biomaterials"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/0192623307310955","article-title":"Safety Evaluation of Ocular Drug Delivery Formulations: Techniques and Practical Considerations","volume":"36","author":"Short","year":"2008","journal-title":"Toxicol. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1167\/iovs.10-6387","article-title":"Pharmacokinetics of a Sustained-Release Dexamethasone Intravitreal Implant in Vitrectomized and Nonvitrectomized Eyes","volume":"52","author":"Burke","year":"2011","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1001\/archopht.125.3.309","article-title":"Randomized Controlled Study of an Intravitreous Dexamethasone Drug Delivery System in Patients With Persistent Macular Edema","volume":"125","author":"Kuppermann","year":"2007","journal-title":"Arch. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1001\/archophthalmol.2010.21","article-title":"Randomized Controlled Trial of an Intravitreous Dexamethasone Drug Delivery System in Patients With Diabetic Macular Edema","volume":"128","author":"Haller","year":"2010","journal-title":"Arch. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1016\/j.ophtha.2010.03.032","article-title":"Randomized, Sham-Controlled Trial of Dexamethasone Intravitreal Implant in Patients with Macular Edema Due to Retinal Vein Occlusion","volume":"117","author":"Haller","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1097\/ICU.0b013e3281108000","article-title":"Drug delivery methods for posterior segment disease","volume":"18","author":"Hsu","year":"2007","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1167\/iovs.08-2969","article-title":"Poly-epsilon-caprolactone intravitreous devices: An in vivo study","volume":"50","author":"Fialho","year":"2009","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0169-409X(01)00200-9","article-title":"Biodegradable microspheres for vitreoretinal drug delivery","volume":"52","author":"Refojo","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1097\/00006982-200410000-00002","article-title":"Risks of Intravitreous Injection: A Comprehensive Review","volume":"24","author":"Jager","year":"2004","journal-title":"Retina"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/ceo.13702","article-title":"Local delivery of corticosteroids in clinical ophthalmology: A review","volume":"48","author":"Fung","year":"2020","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1002\/jps.23387","article-title":"Characterization of Human Sclera Barrier Properties for Transscleral Delivery of Bevacizumab and Ranibizumab","volume":"102","author":"Wen","year":"2013","journal-title":"J. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2147\/LRA.S16314","article-title":"Sub-Tenon\u2019s anesthesia: An update","volume":"5","author":"Guise","year":"2012","journal-title":"Local Reg. Anesth."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1111\/aos.13448","article-title":"Preliminary study of a controllable device for subtenon drug infusion in a rabbit model","volume":"95","author":"Duan","year":"2017","journal-title":"Acta Ophthalmol."},{"key":"ref_21","first-page":"961","article-title":"Drug delivery for posterior segment eye disease","volume":"41","author":"Geroski","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1080\/10717544.2016.1264498","article-title":"Controllable continuous sub-tenon drug delivery of dexamethasone disodium phosphate to ocular posterior segment in rabbit","volume":"24","author":"Huang","year":"2017","journal-title":"Drug Deliv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"101639","DOI":"10.1016\/j.jddst.2020.101639","article-title":"Dexamethasone pharmacokinetics characteristics via sub-tenon microfluidic system in uveitis rabbits","volume":"57","author":"Huang","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1167\/iovs.08-2920","article-title":"A Single Intraoperative Sub-Tenon\u2019s Capsule Injection of Triamcinolone and Ciprofloxacin in a Controlled-Release System for Cataract Surgery","volume":"50","author":"Paganelli","year":"2009","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1016\/j.biopha.2018.08.138","article-title":"A review on recent drug delivery systems for posterior segment of eye","volume":"107","author":"Nayak","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ejpb.2005.11.007","article-title":"Sterilization of gentamicin containing collagen\/PLGA microparticle composites","volume":"63","author":"Friess","year":"2006","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1208\/s12249-009-9226-1","article-title":"Formulation and Performance Characterization of Radio-Sterilized \u201cProgestin-Only\u201d Microparticles Intended for Contraception","volume":"10","author":"Puthli","year":"2009","journal-title":"AAPS PharmSciTech"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/S0939-6411(03)00104-8","article-title":"Mathematical modeling of drug release from bioerodible microparticles: Effect of gamma-irradiation","volume":"56","author":"Faisant","year":"2003","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0168-3659(99)00118-2","article-title":"Gamma irradiation for terminal sterilization of 17beta-estradiol loaded poly-(D,L-lactide-co-glycolide) microparticles","volume":"61","author":"Mohr","year":"1999","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jconrel.2004.06.004","article-title":"Study of gamma-irradiation effects on aciclovir poly(d,l-lactic-co-glycolic) acid microspheres for intravitreal administration","volume":"99","author":"Negro","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/polb.1986.090240215","article-title":"Solute and penetrant diffusion in swellable polymers. II. Verification of theoretical models","volume":"24","author":"Korsmeyer","year":"1986","journal-title":"J. Polym. Sci. Part B Polym. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/polb.1986.090240214","article-title":"Solute and penetrant diffusion in swellable polymers. I. Mathematical modeling","volume":"24","author":"Korsmeyer","year":"1986","journal-title":"J. Polym. Sci. Part B Polym. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hellen, J., and Baker, R. (1980). Theory and Practice of Controlled Drug Delivery from Bioerodible Polymers, Academic Press. Controlled Release of Bioactive Materials.","DOI":"10.1016\/B978-0-12-074450-3.50005-X"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0168-3659(87)90035-6","article-title":"A simple equation for description of solute release II. Fickian and anomalous release from swellable devices","volume":"5","author":"Ritger","year":"1987","journal-title":"J. Control. Release"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0168-3659(87)90034-4","article-title":"A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs","volume":"5","author":"Ritger","year":"1987","journal-title":"J. Control. Release"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1023\/A:1026464124412","article-title":"Biodegradable PLGA Microspheres Loaded with Ganciclovir for Intraocular Administration. Encapsulation Technique, in Vitro Release Profiles, and Sterilization Process","volume":"17","author":"Ramirez","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0939-6411(03)00096-1","article-title":"Biodegradable microparticles for sustained release of a new GnRH antagonist--part I: Screening commercial PLGA and formulation technologies","volume":"56","author":"Schwach","year":"2003","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/S0142-9612(02)00615-4","article-title":"Sustained release system for highly water-soluble radiosensitizer drug etanidazole: Irradiation and degradation studies","volume":"24","author":"Yip","year":"2003","journal-title":"Biomaterials"},{"key":"ref_39","first-page":"31","article-title":"1. Commentary on an exponential model for the analysis of drug delivery: Original research article: A simple equation for description of solute release: I II. Fickian and non-Fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs, 1987","volume":"190","author":"Peppas","year":"2014","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/jcp.10238","article-title":"Inhibition of protein kinase C decreases prostaglandin-induced breakdown of the blood-retinal barrier","volume":"195","author":"Saishin","year":"2003","journal-title":"J. Cell Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jconrel.2015.05.279","article-title":"Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology","volume":"211","author":"Zong","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_42","unstructured":"G\u00f3mez-Ballesteros, M., Andr\u00e9s-Guerrero, V., Parra, F., Marinich, J., De-las-Heras, B., Molina-Mart\u00ednez, I.T., Vazquez, B., San Rom\u00e1n, F., and Herrero-Vanrell, R. (2015, January 5). HEMA\/Bayfit-MA nanoparticles improve the hypotensive effect of acetazolamide in rabbit eyes. Proceedings of the International Forum on Advances in Pharmaceutical Technology, Santiago de Compostela, Spain."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.preteyeres.2014.04.002","article-title":"The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies","volume":"42","year":"2014","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.biomaterials.2017.02.006","article-title":"Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats","volume":"124","author":"Peters","year":"2017","journal-title":"Biomaterials"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jconrel.2004.01.011","article-title":"Effect of the size of biodegradable microparticles on drug release: Experiment and theory","volume":"96","author":"Siepmann","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0168-3659(98)00170-9","article-title":"Tetracycline-HCl-loaded poly(DL-lactide-co-glycolide) microspheres prepared by a spray drying technique: Influence of gamma-irradiation on radical formation and polymer degradation","volume":"59","author":"Bittner","year":"1999","journal-title":"J. Control. Release"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/02713680600719036","article-title":"Safety and Pharmacokinetics of an Intravitreal Biodegradable Implant of Dexamethasone Acetate in Rabbit Eyes","volume":"31","author":"Fialho","year":"2006","journal-title":"Curr. Eye Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1167\/iovs.05-0531","article-title":"Single Periocular Injection of Celecoxib-PLGA Microparticles Inhibits Diabetes-Induced Elevations in Retinal PGE2, VEGF, and Vascular Leakage","volume":"47","author":"Amrite","year":"2006","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2147\/OPTH.S15783","article-title":"Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema","volume":"5","author":"Kuppermann","year":"2011","journal-title":"Clin. Ophthalmol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"877","DOI":"10.2217\/fmb.11.73","article-title":"Ocular herpes simplex virus: How are latency, reactivation, recurrent disease and therapy interrelated?","volume":"6","author":"Clerkin","year":"2011","journal-title":"Futur. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/0002-9394(76)90669-3","article-title":"Increased Intraocular Pressure Induced by Repository Corticosteroids","volume":"82","author":"Herschler","year":"1976","journal-title":"Am. J. Ophthalmol."},{"key":"ref_52","first-page":"13","article-title":"Steroid induced glaucoma and cataract","volume":"37","author":"Mohan","year":"1989","journal-title":"Indian J. Ophthalmol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ejphar.2005.02.019","article-title":"Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model","volume":"511","author":"Ayalasomayajula","year":"2005","journal-title":"Eur. J. Pharmacol."},{"key":"ref_54","first-page":"665","article-title":"Ganciclovir-loaded polymer microspheres in rabbit eyes inoculated with human cytomegalovirus","volume":"38","author":"Veloso","year":"1997","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1002\/jbm.820190315","article-title":"Biodegradation of and tissue reaction to 50:50 poly(DL-lactide-co-glycolide) microcapsules","volume":"19","author":"Visscher","year":"1985","journal-title":"J. Biomed. Mater. Res."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/2\/228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:20:40Z","timestamp":1760160040000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/13\/2\/228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,6]]},"references-count":55,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["pharmaceutics13020228"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics13020228","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,6]]}}}