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Memantine‐Loaded PEGylated Biodegradable Nanoparticles for the Treatment of Glaucoma
Author(s) -
SánchezLópez Elena,
Egea Maria Antonia,
Davis Benjamin Michael,
Guo Li,
Espina Marta,
Silva Amelia Maria,
Calpena Ana Cristina,
Souto Eliana Maria Barbosa,
Ravindran Nivedita,
Ettcheto Miren,
Camins Antonio,
García Maria Luisa,
Cordeiro Maria Francesca
Publication year - 2018
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201701808
Subject(s) - memantine , glaucoma , nmda receptor , pharmacology , neuroprotection , in vivo , excitotoxicity , medicine , glutamate receptor , chemistry , ophthalmology , receptor , biology , microbiology and biotechnology
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.