Abstract

AbstractPurposeAlzheimer’s disease (AD) is the major cause of dementia in the world with increasing evidence of the retina being affected. Since no cure exists, the development of new treatments is an urgent unmet need. Curcumin, a natural polyphenol found in curry, has been advocated as a potential neuroprotectant in AD. However, its poor solubility in water and low bioavailability, have limited its clinical translation. In this study we describe a novel curcumin nanoparticle (CN) formulation and evaluate its neuroprotective efficacy in vitro and in vivo.MethodsCNs were formulated using a thin film rehydration technique. R28 cells were used to assess CN neuroprotective activity. For in vivo studies 10‐month‐old 3xTg‐AD mice were treated intranasally 5 days/week with 3 μl of either CNs (n = 7) or vehicle (n = 6). After three months of treatment, animals had DARC (Detection of Apoptosing Retinal Cells) imaging and their brains (amyloid‐beta) were immunostained. All results are given with the standard error and the statistical test used is a student T‐test.ResultsCN formulation incorporating over 4 mg/ml of curcumin was stable over 90 days. CNs protected R28 cells against a) glutamate excitotoxicity with an IC50 of 22.36 ± 0.50 mm versus 4.54 ± 0.32 mm for control group (p < 0.0001) and b) hypoxia mimetic cobalt chloride with an IC50 of 427.9±37.62 μm versus 259.4 ± 15.34 μm for control group (p < 0.05). No adverse effects were seen in vivo either systemically or in the eye. 3xTg‐AD mice receiving CNs were found to have a significant reduction in the DARC count (p < 0.05) compared to vehicle controls (17.36 ± 3.34 versus 49.08 ± 13.28). Their brains had a reduction in Aβ deposition score compared to vehicle controls (3.61 ± 0.17 versus 4.47 ± 0.23, p < 0.01).ConclusionsThese promising results suggest that systemic CN has a potential therapeutic effect in AD, and that the effects of AD therapy can be assessed through the eye.

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