NANOMEDICINE IN NEUROSCIENCE: THE POTENTIAL OF TARGETED NANOPARTICLES IN NEURODEGENERATIVE DISORDERS

Pathologic conditions affecting the brain such as neurodegenerative diseases and neurological disorders (i.e. Parnkison’s disease, Alzheimer’s disease, Huntington disease, multiple sclerosis, brain tumors, etc.) are amongst the most un-treatable syndromes. A major obstacle for the application of therapeutics is that a great number of pharmacologically active molecules (estimated 98%) are not able to reach the Central Nervous System (CNS) and to exert their activity as they cannot cross the Blood-Brain Barrier (BBB). Thus, one of the challenges of pharmaceutical research nowadays is to discover tools enabling an effective and efficacious delivery of drugs into the CNS. Non-invasive techniques based on colloidal carriers (nanomedicine) could represent a huge potential and, in line with the overall increase in knowledge and nanotechnologies, surface engineering of nano-sized carriers is now representing the cutting edge of nanomedicine, leading to the production of selectively targeted therapies based on targeted nanocarriers. In fact, achieving nanocarriers able to be stable in the blood-stream, to protect the drug from metabolism and to promote a long-lasting release of the drug, is still a pivotal pre-requisite for nanomedicine, but it is now to be considered as “not enough”. Active targeting to specific pathological cells is now the challenge of pharmaceutical nanotechnologists, who are facing with difficulties in colloidal chemistry and most of all in the characterization of the engineered nanocarriers from a technological and physiological points of view. As an example, the application of nanotechnology to brain-related disorders, called nanoneuromedicine, is certainly representing one of the most stimulating as well as one of the most difficult challenges, due to the presence of biological barriers (BBB) and the great variability in BBB permeability depending on the chosen disease. Nevertheless, encouraging results have been obtained demonstrating the possibility of targeting the CNS up to reaching a significant percentage in brain localization of nanocarriers. As an example of targeted NPs, new targeted polymeric poly-lactide-co-glycolide (PLGA) NPs modified with glycopeptides (g7-NPs) have been recently demonstrated, by in vivo and in vitro experiments, to be able to trigger brain delivery of active substances (brain accumulation up to 10-15% of the injected dose). Moreover, BBB crossing of g7-NPs was recently assessed by our team, evidencing endocytosis/macropinocytosis pathways as preferential mechanisms for g7-NPs movements and interactions. With this work, we will also show new developments and insights of our research with highlights mainly on g7-NPs in vitro behavior on neurons/glia as well as in vivo (rodents) brain localization and trafficking after different routes of administration. Notwithstanding these results, it is our opinion that in order to obtain a real progress in neurological disorders’ therapy based on innovative and non invasive protocols (i.e. nanomedicine), a team effort is highly desired. The interdisciplinary competences and skills of all the experts in Neuro-diseases and Nano-Technology (from neurobiologists to neurophysiologists, from nanotechnologists to physicians) must be shared, discussed, considered and applied, thus paving the way to new vistas in treatments and most of all for the correct development of this field of research.