Transferrin-Functionalized Liposomes for the Delivery of Gallic Acid: A Therapeutic Approach for Alzheimer's Disease.

Abstract

Senile plaques composed of amyloid β (Aβ) fibrils are considered the leading cause of Alzheimer’s disease (AD). Molecules with the ability to inhibit Aβ aggregation and/or promote Aβ clearance are thus a promising approach for AD therapy. Our group recently demonstrated that gallic acid (GA) has strong anti-amyloidogenic properties. In this study, stealth liposomes were prepared for the delivery of GA for AD therapy. The liposomes were functionalized with transferrin (Tf) to direct them to the brain, since Tf receptors are overexpressed in the endothelial cells of the blood–brain barrier. GA-loaded Tf-functionalized liposomes showed mean diameters of 130 nm, low polydispersity index values, and neutral zeta potential. Moreover, the produced nanocarriers promoted the sustained release of GA over 5 days and are physically stable for 1 month under storage conditions. Furthermore, GA-loaded Tf-functionalized liposomes showed a strong ability to interact with Aβ1-42 monomers, slowing down the Aβ monomer-to-oligomer and oligomer-to-fibril transitions and decreasing the number of fibrils formed by 56%. In addition, the NPs disaggregated approximately 30% of preformed Aβ fibrils. The presented results suggest that Tf-functionalized liposomes could be a viable platform for the brain delivery of GA for AD therapy. Studies with animal models of AD will be valuable for validating the therapeutic efficacy of this novel liposomal formulation.