A Potential Therapy for Alzheimer’s Disease: Encapsulation of Curcumin Within Polymeric PLGA-PEG Nanoparticles Protects Neuro2A cells From Beta-Amyloid Induced Cytotoxicity and Improves Bioavailability
Alzheimer’s disease (AD) is characterized by accumulation of beta-amyloid (BA) plaques in the brain and activation of caspase pathway, both of which lead to neuronal apoptosis. Since currently available medications are not very promising, there is an increased need for a versatile drug with multifunctional properties. Curcumin, a principal curcuminoid of turmeric, has anti-amyloid, anti-apoptotic, and antioxidant activities, all of which are important in AD treatment. However, curcumin’s water insolubility and poor bioavailability limit its efficacy in AD. Nanoparticle-based drug delivery approaches to circumvent the pitfalls of curcumin’s poor solubility have been studied in cancer, but not in AD. The goal of this project is to use a novel polymeric nanoparticle (PEG-PLGA) encapsulated curcumin as an effective vehicle for curcumin delivery to an in vitro AD neuronal cell model and to study its anti-apoptotic and anti-amyloid effects. We predicted that nanocurcumin would be able to mitigate the βA induced cytotoxicity by attenuating Caspase-3 activity.
Results from this study demonstrated that 20μM PEG-PLGA nanoparticle encapsulated curcumin (nanocurcumin) reduced βA levels by around 30% (p<0.05), exhibited antioxidant activity of 90%, and increased cell viability by over 20% when compared to curcumin. Moreover, the 24-hour in vitro release kinetics of nanocurcumin demonstrated a 70% curcumin release from nanoparticles, and fluorescence microscopy images showed that nanocurcumin had a higher cellular uptake than did curcumin. While previous studies have identified the therapeutic use of curcumin, this study is the first to use a polymeric nanoparticle vehicle for curcumin delivery in a cell model of AD.