Improved Cognitive Impairment Through PLGA Nanocrystal-Based Drug Delivery of Curcumin and Piperine in Alzheimer's Disease Model

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease that causes dementia, impaired cognitive function, and disorientation. Studies have revealed that curcumin and piperine were found to be neuroprotective for patients with dementia. Nevertheless, both compounds are known for their poor solubility. To address issues related to poor bioavailability, nanocrystals of curcumin and piperine in combination were fabricated and characterized by physicochemical, surface morphology, drug excipient compatibilities, and bioavailability studies. The nanocrystal with the highest bioavailability was selected for pharmacokinetics and pharmacodynamics studies. Optimized nanocrystals of PLGA co-loaded curcumin and piperine (FNC) were successfully developed using emulsion diffusion-high pressure homogenization-solvent evaporation (EHS) technique with Poloxamer 188 as the stabilizer. Among nine formulations, optimized FNC1 had a particle size of 116.6 ± 2.13 nm and zeta potential at -27.9 ± 1.51 mV. Saturation solubility and in vitro drug release studies demonstrated enhanced solubility of curcumin and piperine in FNC1 as compared to pure compounds. Oral administration of optimized FNC1 in streptozotocin (STZ)-induced AD rat model was presented with significant improvement of spatial memory from both the Morris Water Maze and Passive Avoidance test. Further histology studies by staining the cortex and hippocampus regions were presented with a significantly reduced number of pyramidal cells with extensive nuclear pyknosis and degeneration that was previously seen in untreated STZ-induced AD rats. It was concluded from this study that the nanocrystals developed in this study had improved the solubility and bioavailability of curcumin and piperine which then improved the memory impairment in STZ-induced AD rats.