Using DARC to assess neuroprotection of curcumin eyedrops in a glaucoma model

Abstract

Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5dione) is a polyphenol extracted from turmeric that has long been advocated for the treatment of a variety of conditions including neurodegenerative and infammatory disorders. Despite this promise, the clinical use of curcumin has been limited by the poor solubility and low bioavailability of this molecule. In this article, we describe a novel nanocarrier formulation comprising Pluronic-F127 stabilised D-α-Tocopherol polyethene glycol 1000 succinate nanoparticles, which were used to successfully solubilize high concentrations (4.3mg/mL) of curcumin. Characterisation with x-ray difraction and in vitro release assays localise curcumin to the nanocarrier interior, with each particle measuring <20nm diameter. Curcumin-loaded nanocarriers (CN) were found to signifcantly protect against cobalt chloride induced hypoxia and glutamate induced toxicity in vitro, with CN treatment signifcantly increasing R28 cell viability. Using established glaucoma-related in vivo models of ocular hypertension (OHT) and partial optic nerve transection (pONT), topical application of CN twice-daily for three weeks signifcantly reduced retinal ganglion cell loss compared to controls. Collectively, these results suggest that our novel topical CN formulation has potential as an efective neuroprotective therapy in glaucoma and other eye diseases with neuronal pathology.