Title : Transferrin-modified nanoparticles for Alzheimer's disease therapy with natural compounds
Abstract:
Alzheimer's disease (AD) is an incurable neurological disease and the primary cause of dementia, characterized by amyloid β (Aβ) fibril deposits. Caffeic acid (CA) has shown the ability to prevent Aβ fibril formation and disaggregate mature Aβ fibrils. However, its chemical instability and low bioavailability limit CA’s in vivo therapeutic activity. To overcome these limitations, liposomes containing CA were prepared. The surface of the nanoparticles (NPs) was modified with transferrin (Tf), intending the dual-targeting of CA to the blood-brain barrier and neuronal cells. The optimized brain-targeted drug delivery system (DDS) had a mean size of 140 nm, a polydispersity index lower than 0.2, and zeta potential values close to 0 mV, making it appropriate for brain delivery. Tf-modified NPs showed a suitable encapsulation efficiency and physical stability under storage conditions for 2 months. Furthermore, in simulated physiological conditions, the DDS enabled the sustained release of CA for 5 days. The therapeutic activity of the DDS was investigated in terms of anti-amyloidogenic properties using an in vitro model of AD. The findings reveal that CA-loaded Tf-modified NPs can prevent Aβ fibrillation and disrupt preformed fibrils. Thus, the developed brain-targeted DDS may be a promising strategy to prevent and treat AD.
