Neurodegenerative diseases are caused by the progressive death of neurons in different regions of the nervous system. Among these, Alzheimer's disease (AD) is caused by progressive formation of senile plaques and neurofibrillary tangles in the cerebral cortex, as well as the loss of neurons and synapses. The risk of suffering a neurodegenerative disease increases with age, this situation creates a critical need to improve develop new approaches for its treatment.

The N-terminal c-Jun kinases present different isoforms JNK1, JNK2 and JNK3, which are involved in the loss of neuronal cells in neurodegenerative diseases. Licochalcone-A (Lic-A), a novel flavonoid, has an inhibitory effect on the activity of JNK1 and could inhibit JNK3. In this way, it could become an innovative alternative to neurodegenerative treatment. However, the presence of the blood-brain barrier (BBB), due to its high selectivity, becomes a limiting factor for drugs to reach the brain tissues.

Nanoparticles (NPs) are colloidal systems of particular interest for drug transport increasing accumulation at the target site and achieving controlled release of the drug. The functionalization of NPs with cell penetrating peptides (CPPs) has attracted attention, because it increases their internalization efficiency in the cell membrane, improving their pass across barriers.

In this research, polymeric PLGA-NPs of Lic-A were developed by solvent displacement method. Particle surface was functionalized with CPPs, manually synthesized in solid phase, selected for their affinity for receptors on endothelial cells of BBB (B6 peptide) and neuronal cells (TET-1-Cys peptide). These NPs could constitute a newfangled therapeutic alternative for AD.