Folic acid-conjugated amphiphilic copolymers for the enhanced delivery of donepezil: synthesis, characterization and blood-brain barrier permeability in a co-culture model.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic options, largely due to challenges in delivering drugs across the blood-brain barrier (BBB). In this study, we synthesized folic acid (FA) conjugated amphiphilic copolymers via reversible addition-fragmentation chain transfer (RAFT) polymerization to enhance the targeted delivery of donepezil (DZP) to the brain. The copolymers were self-assembled into micelles and extensively characterized for their size, zeta potential, and stability using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The micelles were further evaluated for their ability to cross an in vitro BBB model and their cellular uptake by brain endothelial cells. FA conjugation was employed to exploit the folate receptor-mediated transport mechanism, which has shown potential for improving drug delivery across the BBB. This study demonstrates the feasibility of using FA functionalized micelles as a targeted delivery system, offering potential advancements in the treatment of Alzheimer's disease.