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Shiama Indu Balendra, Benjamin Davies, Li Guo, M Francesca Cordeiro; Eye-drop formulation and Evaluation of Micellar Curcumin for the treatment of glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2550.
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Glaucoma is a multifactorial neurodegenerative disease; however current treatment options consist of only intra-ocular pressure lowering agents. Neuroprotective agents have the potential to fill the gap in treatment of normotensive glaucoma. Curcumin has demonstrated neuroprotective potential, however its biological usage is challenged by its poor water solubility and stability at physiological pH. We hypothesized that curcumin could be solubilized into a micellar formulation with high encapsulation efficiency and >30 day stability in phosphate buffer solution, and that this formulation would demonstrate a neuroprotective effect in vitro and in vivo upon topical administration in a well-established experimental rat model of glaucoma.
A thin-film hydration technique was employed to manufacture curcumin loaded micelles which were characterised for size and dispersity using dynamic light scattering and transmission electron microscopy. Encapsulation efficiency and curcumin degradation was assessed spectroscopically. Stability of the formulation was assessed by measuring changes in particle physical properties and encapsulation efficiency over time. Assessment of curcumin mediated neuroprotection in vitro was achieved using an alamarBlue cell-viability assay in paraquat-treated primary RGCs. In vivo assessment of topical curcumin micelle mediated neuroprotection was assessed in the well-established ocular hypertensive rat model with primary endpoints of DARC (Detection of Apoptosing Retinal Cells) imaging and whole retinal Brn3a histology.
A micellar formulation of curcumin was prepared containing ~4.0 mg/mL with >90% encapsulation efficiency. Formulation was found to be stable at room temperature for over 30 days which increased to >60 days with lyophilisation in the presence of a cryoprotectant. Curcumin was found to elicit significant neuroprotection in vitro (p<0.05) and was found to be well tolerated after 3 weeks of topical instillation in vivo. Significant neuroprotection was observed versus controls in vivo.
A novel method to solubilize curcumin to 4 mg/mL is described which is stable for >60 days when stored at room temperature with minimal product degradation. This curcumin formulation could be beneficial not only as adjunctive therapy in glaucoma but also in other neurodegenerative disorders via alternative modes of administration.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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