Brain targeting with polymeric nanoparticles: which administration route should we take?

Polymeric nanoparticles (NPs) represent one of the most studied carriers for drug delivery, due to their ability in overcoming problems related to the instability of drugs and their widespread biodistribution as well as for the possibility of targeting cells or organs [1]. In particular, drug delivery to the brain is a challenge for scientists, since the Blood Brain Barrier (BBB) allows the entrance of specific and selected molecules, but it hampers the passage of a remarkable number of pharmacologically active molecules. A plethora of strategies aims to create, characterize and test in vitro and in vivo NPs able to cross the BBB, in health or diseased state, i.e. with physiological or enhanced permeability [2]. Nearly all the strategies involved are based on moieties, as surfactants, antibodies, ligands for receptors and peptides [3-7] linked on the NPs surface (engineered NPs). Beside the “BBB crossing aim”, NPs targeted to the Central Nervous System (CNS) have to be planned considering their “journey into the body” [8], as the biodistribution of the nanocarriers and the route of administration is another aspect to be taken into account.