Targeted liposomal epigallocatechin delivery for Alzheimer's disease: Effect on amyloid β fibrillation and neutralization of free radicals.

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition marked by amyloid β (Aβ) plaque accumulation, contributing to cognitive decline. Epigallocatechin (EGC) has shown potential in preventing Aβ aggregation and disrupting fibrils, but its low bioavailability and poor blood-brain barrier (BBB) penetration limit its therapeutic use. To address these challenges, this study introduces the first functionalized nanosystem developed for the EGC delivery. Liposomal EGC was optimized and conjugated with transferrin (Tf), given literature evidence supporting its potential role in BBB-targeting strategies. The optimal formulation exhibited a mean diameter of 127 ± 14 nm, a polydispersity index of 0.20 ± 0.02, a zeta potential of -0.9 ± 0.3 mV, and an encapsulation efficiency of 20 ± 3%, properties that were maintained after 1 month of storage at 4 °C. Moreover, the nanosystem exhibited a controlled and sustained release, achieving 77 ± 11% release over 9 days. In terms of therapeutic activity, the nanoformulation showed an antioxidant capacity of 53 ± 6%, demonstrating its potential to neutralize free radicals, a key factor in AD progression. Furthermore, targeted liposomal EGC completely inhibited Aβ fibrillation, as demonstrated by thioflavin T assays. Data revealed a reduction in parallel β-sheet content from 44 ± 4% to 33 ± 5% and an increase in α-helices from 31 ± 5 to 45 ± 4%, suggesting inhibition of fibril formation. Additionally, Tf conjugation enhanced liposome uptake by endothelial cells without inducing cytotoxicity. These findings support the potential of this nanosystem as a promising platform for further investigation in AD.