Brain targeting by engineered nanoparticles: in vivo and in vitro evidences

In the last years, the application of "nanotechnology“ to the field of “medicine” surely represented the most innovative strategy to cope with diseases and could be named as nanomedicine, which is mostly applied to difficult-to-treat diseases. In this field of research, the most important goal to be reached is an increase in selectivity and specificity of drug-action. Several results with stimulating findings in preclinical or clinical phases have been obtained using nanocarriers delivering agents to targeted pathologies, and among them, it is known that neuro-pathologies represent a stimulating issue. In fact, the pharmaceutical treatment of Central Nervous System (CNS) disorders is the second largest area of therapy, following cardiovascular diseases. Nowadays, non-invasive drug delivery systems for CNS are actively studied. The nano-technological approach consists of the use of nanosystems (colloidal carriers), which could be polymer-based (nanoparticles, Np) or solid lipid material made (solid lipid nanoparticles, SLNp) and lipid-based (liposomes, LP). In fact, the development of these new delivery systems started with the discovery that properly surface-engineered colloidal vectors, with a diameter around 200 nm, are able to cross the BBB without causing apparent damage, and to deliver drugs or genetic materials into the brain. During this talk, an overview will be presented considering the most recent literature results of nanomedicine applied to brain diseases, focusing in particular on peptide-decorated nanosystems able to target the CNS.In vitro and in vivo experiments allowed to establish a pathway through which engineered NPs can cross the BBB and showed the possible NPs’ transport from cell to cell inside the CNS and the possible tropism of NPs for specific neuronal cell populations.References• A.M. Grabrucker, C. C. Garner, T.M. Boeckers, L. Bondioli, B. Ruozi, F.Forni, M.A. Vandelli, G.Tosi , Development of novel Zn2+ loaded nanoparticles designed for cell-type targeted drug release in CNS neurons: in vitro evidences. PLOS ONE, 2011, Vol 6, e17851.• G. Tosi, R.A. Fano, L. Badiali, R. Benassi, F. Rivasi, B. Ruozi, F. Forni, M.A., Vandelli. Investigation on the mechanisms for Blood-Brain Barrier crossing of brain-targeted glycopeptides nanoparticles, Nanomedicine UK, 2011, 6(3), 423-436• G. Tosi, AV Vergoni, B. Ruozi, L. Bondioli, L. Badiali, F. Rivasi, L. Costantino, F. Forni, M.A. Vandelli, Sialic-acid and glycopeptides conjugated PLGA nanoparticles for Central Nervous System targeting: in vivo pharmacological evidence and biodistribution, Journal of Controlled Release, 2010,145, 49-57.