Improved cognition and memory via PLGA nanoparticle-mediated delivery of curcumin and piperine in an in vivo Alzheimer's disease model.

Abstract

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, polymeric nanoparticles loaded with curcumin and piperine, in combination, were fabricated and characterized through physicochemical, surface morphology, drug-excipient compatibility, and bioavailability studies. The nanoparticle with the highest bioavailability was selected for pharmacokinetics and pharmacodynamics studies. Optimized Poly (D, L-lactide-co-glycolide) nanoparticles loaded with curcumin and piperine, which we refer to as functional nanoparticles (FNP), were successfully developed using the emulsion diffusion-high-pressure homogenization-solvent evaporation (EHS) technique with Poloxamer 188 as the stabilizer. Among nine formulations obtained, FNP1 had a particle size of 116.6 ± 2.13 nm and a zeta potential of -27.9 ± 1.51 mV. Saturation solubility and in vitro drug release studies demonstrated an enhanced solubility of curcumin and piperine in FNP1 compared to the pure compounds. Oral administration of FNP1 in a streptozotocin (STZ)-induced AD rat model resulted in significant improvement of spatial memory, as demonstrated by both the Morris Water Maze and Passive Avoidance tests. Further histology studies, which involved staining the cortex and hippocampus regions, revealed a significantly reduced number of pyramidal cells with extensive nuclear pyknosis and degeneration, a finding previously observed in untreated STZ-induced AD rats. This study concluded that the polymeric nanoparticle developed, FNP1, had successfully improved the solubility and bioavailability of curcumin and piperine, thereby enhancing cognitive and memory impairment in STZ-induced AD rats.