Neuroprotective and Neurorescue Effects of a Novel Polymeric Nanoparticle Formulation of Curcumin (NanoCurc (TM)) in the Neuronal Cell Culture and Animal Model: Implications for Alzheimer's Disease

Alzheimer's disease (AD) is characterized by deposition of amyloid-beta (A beta) plaques within the brain parenchyma followed by synaptic loss and neuronal death. Deposited A beta reacts with activated microglia to produce reactive oxygen species (ROS) and cytochemokines, which lead to severe neuroinflammation. Curcumin is a yellow polyphenol compound found in turmeric, a widely used culinary ingredient that possesses anti-inflammatory and anti-cancer properties and may show efficacy as a potential therapeutic agent in several neuro-inflammatory diseases including AD. However, poor aqueous solubility and sub-optimal systemic absorption from the gastrointestinal tract may represent factors contributing to its failure in clinical trials. To increase curcumin's bioavailability, a polymeric nanoparticle encapsulated curcumin (NanoCurc (TM)) was formulated which is completely water soluble. NanoCurc (TM) treatment protects neuronally differentiated human SK-N-SH cells from ROS (H2O2) mediated insults. NanoCurc (TM) also rescues differentiated human SK-N-SH cells, which were previously insulted with H2O2. In vivo, intraperitoneal (IP) NanoCurc (TM) injection at a dose of 25 mg/kg twice daily in athymic mice resulted in significant curcumin levels in the brain (0.32 mu g/g). Biochemical study of NanoCurc (TM)-treated athymic mice revealed decreased levels of H2O2 as well as caspase 3 and caspase 7 activities in the brain, accompanied by increased glutathione (GSH) concentrations. Increased free to oxidized glutathione (GSH : GSSH) ratio in athymic mice brain versus controls also indicated a favorable redox intracellular environment. Taken together, these results suggest that NanoCurc (TM) represents an optimized formulation worthy of assessing the therapeutic value of curcumin in AD.