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Increasing reports of similarities in glaucoma and other neurodegenerative conditions have led to speculation that therapies for brain neurodegenerative disorders may also have potential as glaucoma therapies. Memantine is an <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate (NMDA) antagonist approved for Alzheimer's disease treatment. Glutamate\u2010induced excitotoxicity is implicated in glaucoma and NMDA receptor antagonism is advocated as a potential strategy for RGC preservation. This study describes the development of a topical formulation of memantine\u2010loaded PLGA\u2010PEG nanoparticles (MEM\u2010NP) and investigates the efficacy of this formulation using a well\u2010established glaucoma model. MEM\u2010NPs &lt;200 nm in diameter and incorporating 4 mg mL<jats:sup>\u22121<\/jats:sup> of memantine were prepared with 0.35 mg mL<jats:sup>\u22121<\/jats:sup> localized to the aqueous interior. In vitro assessment indicated sustained release from MEM\u2010NPs and ex vivo ocular permeation studies demonstrated enhanced delivery. MEM\u2010NPs were additionally found to be well tolerated in vitro (human retinoblastoma cells) and in vivo (Draize test). Finally, when applied topically in a rodent model of ocular hypertension for three weeks, MEM\u2010NP eye drops were found to significantly (p &lt; 0.0001) reduce RGC loss. These results suggest that topical MEM\u2010NP is safe, well tolerated, and, most promisingly, neuroprotective in an experimental glaucoma model.<\/jats:p>","DOI":"10.1002\/smll.201701808","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T13:04:43Z","timestamp":1511183083000},"source":"Crossref","is-referenced-by-count":100,"title":["Memantine\u2010Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma"],"prefix":"10.1002","volume":"14","author":[{"given":"Elena","family":"S\u00e1nchez\u2010L\u00f3pez","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry Faculty of Pharmacy Institute of Nanoscience and Nanotechnology (IN2UB) University of Barcelona  Barcelona 08028 Spain"},{"name":"Biomedical Research and Networking Center in Neurodegenerative diseases (CIBERNED)  Madrid 28031 Spain"}]},{"given":"Maria Antonia","family":"Egea","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry Faculty of Pharmacy Institute of Nanoscience and Nanotechnology (IN2UB) University of Barcelona  Barcelona 08028 Spain"}]},{"given":"Benjamin Michael","family":"Davis","sequence":"additional","affiliation":[{"name":"Glaucoma and Retinal Neurodegeneration Research Visual Neuroscience UCL Institute of Ophthalmology  Bath Street London EC1V 9EL UK"}]},{"given":"Li","family":"Guo","sequence":"additional","affiliation":[{"name":"Glaucoma and Retinal Neurodegeneration Research Visual Neuroscience UCL Institute of Ophthalmology  Bath Street London EC1V 9EL UK"}]},{"given":"Marta","family":"Espina","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry Faculty of Pharmacy Institute of Nanoscience and Nanotechnology (IN2UB) University of Barcelona  Barcelona 08028 Spain"}]},{"given":"Amelia Maria","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Biology and Environment School of Life and Environmental sciences (ECVA, UTAD) and Centre for Research and Technology of Agro\u2010Environmental and Biological Sciences (CITAB\u2010UTAD) University of Tr\u00e1s\u2010os\u2010Montes e Alto Douro  Quinta de Prados 5001\u2010801 Vila Real Portugal"}]},{"given":"Ana Cristina","family":"Calpena","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry Faculty of Pharmacy Institute of Nanoscience and Nanotechnology (IN2UB) University of Barcelona  Barcelona 08028 Spain"}]},{"given":"Eliana Maria Barbosa","family":"Souto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology Faculty of Pharmacy University of Coimbra (FFUC) and REQUIMTE\/Group of Pharmaceutical Technology  Polo das Ci\u00eancias da Sa\u00fade Azinhaga de Santa Comba 3000\u2010548 Coimbra Portugal"}]},{"given":"Nivedita","family":"Ravindran","sequence":"additional","affiliation":[{"name":"Glaucoma and Retinal Neurodegeneration Research Visual Neuroscience UCL Institute of Ophthalmology  Bath Street London EC1V 9EL UK"}]},{"given":"Miren","family":"Ettcheto","sequence":"additional","affiliation":[{"name":"Biomedical Research and Networking Center in Neurodegenerative diseases (CIBERNED)  Madrid 28031 Spain"},{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry Faculty of Pharmacy University of Barcelona  Barcelona 08028 Spain"}]},{"given":"Antonio","family":"Camins","sequence":"additional","affiliation":[{"name":"Biomedical Research and Networking Center in Neurodegenerative diseases (CIBERNED)  Madrid 28031 Spain"},{"name":"Department of Pharmacology, Toxicology and Therapeutic Chemistry Faculty of Pharmacy University of Barcelona  Barcelona 08028 Spain"}]},{"given":"Maria Luisa","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology and Physical Chemistry Faculty of Pharmacy Institute of Nanoscience and Nanotechnology (IN2UB) University of Barcelona  Barcelona 08028 Spain"}]},{"given":"Maria Francesca","family":"Cordeiro","sequence":"additional","affiliation":[{"name":"Glaucoma and Retinal Neurodegeneration Research Visual Neuroscience UCL Institute of Ophthalmology  Bath Street London EC1V 9EL UK"},{"name":"Western Eye Hospital Imperial College Healthcare Trust  London UK"}]}],"member":"311","published-online":{"date-parts":[[2017,11,20]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"crossref","first-page":"174","DOI":"10.4103\/2008-322X.183934","volume":"11","author":"Celiker H.","year":"2016","journal-title":"J. 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