Mucoadhesive chitosan-modified PLGA nanoparticles loaded with green tea extract inhibit amyloid β peptide aggregation and oxidative stress

Alzheimer's disease (AD) is associated with amyloid β (Aβ) plaque deposition in the brain, which leads to neurotoxicity through inflammation and oxidative stress. Green tea has shown promise in treating AD due to its anti-amyloidogenic, anti-inflammatory, and antioxidant properties. However, the therapeutic efficacy of green tea extract (GTE) is limited by the low bioavailability of its main constituents and their poor ability to cross the blood-brain barrier. Nanoparticles (NPs) designed for nose-to-brain delivery offer a solution by enhancing the targeted delivery of GTE to the brain. In this study, poly(lactic- co -glycolic) acid (PLGA) NPs modified with chitosan (Ch) were developed for brain delivery of GTE. GTE-loaded Ch-modified PLGA NPs exhibited suitable physicochemical characteristics for brain delivery, including a spherical morphology with an average diameter of 274 ± 15 nm and a uniform size distribution. The NPs showed an encapsulation efficiency of 41 ± 8 % and a positive zeta potential of 9 ± 4 mV. They retained their colloidal stability in storage conditions for up to 3 months, and the release kinetics demonstrated a controlled and sustained release profile, with 32 ± 10 % of GTE released over 6 days. Additionally, the NPs' mucoadhesive properties were confirmed through their interactions with mucin. Importantly, the NPs exhibited strong anti-amyloidogenic activity by effectively preventing Aβ aggregation, along with an antioxidant activity of 88 ± 4 %. This study provides valuable insights into the potential of mucoadhesive PLGA NPs for GTE delivery, representing a significant advancement in therapeutic strategies for managing AD by targeting critical disease mechanisms. • NPs exhibited suitable size, stability, and positive zeta potential. • GTE was released from NPs in a sustained manner for up to 6 days. • Chitosan-modified NPs showed strong mucoadhesive properties. • GTE-loaded NPs prevented Aβ aggregation and showed 88 % antioxidant activity.