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Title: Memantine loaded PEGylated biodegradable nanoparticles for the treatment of glaucoma
Author: Sánchez-López, E. (Elena)
Egea Gras, Ma. Antonia
Davis, Benjamin Michael
Guo, Li
Espina García, Marta
Silva, Amélia M.
Calpena Campmany, Ana Cristina
Souto, Eliana B.
Ravindran, Nivedita
Ettcheto Arriola, Miren
Camins Espuny, Antoni
García López, María Luisa
Cordeiro, M. Francesca
Keywords: Glaucoma
Sistemes d'administració de medicaments
Drug delivery devices
Issue Date: 11-Jan-2018
Publisher: Wiley-VCH
Abstract: Glaucoma is a multifactorial neurodegenerative disease associated with retinal ganglion cells (RGC) loss. 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 N-methyl-d-aspartate (NMDA) antagonist approved for Alzheimer's disease treatment. Glutamate-induced 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-loaded PLGA-PEG nanoparticles (MEM-NP) and investigates the efficacy of this formulation using a well-established glaucoma model. MEM-NPs <200 nm in diameter and incorporating 4 mg mL−1 of memantine were prepared with 0.35 mg mL−1 localized to the aqueous interior. In vitro assessment indicated sustained release from MEM-NPs and ex vivo ocular permeation studies demonstrated enhanced delivery. MEM-NPs 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-NP eye drops were found to significantly (p < 0.0001) reduce RGC loss. These results suggest that topical MEM-NP is safe, well tolerated, and, most promisingly, neuroprotective in an experimental glaucoma model.
Note: Versió postprint del document publicat a:
It is part of: Small, 2018, vol. 14, num. 2, p. 1701808
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ISSN: 1613-6810
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)
Articles publicats en revistes (Institut de Nanociència i Nanotecnologia (IN2UB))

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