Drug delivery to the Central Nervous System (CNS) represents a huge challenge for all neuroscientists owing to the presence of the Blood-Brain Barrier (BBB) hampering the influx to the brain of most of the drugs, enzymes, gene materials. Nanotechnology, based on polymeric nanoparticles (Np) and liposomes, could be an useful tool for the delivery of the drugs in the brain if they are planned for crossing the BBB. This goal can be achieved specifically engineering the Np surface in order to take advantage of the BBB crossing pathways, such as endocytosis or transcytosis. We applied this approach modifying polylactide-co-glycolide (PLGA) Np with two different peptides to produce highly selective nanosystems able to enter the brain after i.v. administration in the rats [Costantino L. et al. (2005). J Control Rel 108, 84-96; Tosi G. et al. (2007) J. Control Rel 122, 1-9]. The administration of decorated Np with a simil-opioid peptide (planned and synthesized in our laboratories) allows a variety of P-glycoprotein substrate to cross the BBB at a rate of 15-20% of the injected dose, as microscopy technique (confocal, fluorescent), biodistribution and pharmacological studies proved [Vergoni A.V. et al. (2009) Nanomedicine (NBM) 5, 369-377] These systems cross the BBB via an endocytic mechanism pointed out by an electron microscopy procedure (fig. 1). On the contrary, the Np decorated with a Leptin fragment should be able to take advantage of specific BBB-leptin receptors (Ob-R). In vivo experiments pointed out the efficacy of these leptin modified Np in the brain delivery and the trancytosis mechanism of the BBB crossing (fig. 2). Any anoretic effect of the Leptin-fragment covering the Np was exclude by food-intake experiments.Figure 1. Left: Electron microscopy image of multiple mechanisms of simil-opioid-Np interaction with BBB endothelial cells; Right: Fig. 2. Brain images after iv administration of Leptin-derived peptide- Np. Red spots are due to Np labeled with TRICT and blue-spots are brain nuclei with DAPI.
|Data di pubblicazione:||2010|
|Titolo:||Peptide-engineered polylactide-co-glycolide (PLGA) nanoparticles for brain delivery of drugs: in vivo experiments and proof of concept|
|Autore/i:||Tosi, Giovanni; Fano, Rita Adriana; Badiali, Luca; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Benassi, Rois; Vandelli, Maria Angela; Forni, Flavio|
|Nome del convegno:||Neuroscience 2010|
|Luogo del convegno:||San Diego, CA, US|
|Data del convegno:||13-17 November 2010|
|Citazione:||Peptide-engineered polylactide-co-glycolide (PLGA) nanoparticles for brain delivery of drugs: in vivo experiments and proof of concept / Tosi, Giovanni; Fano, Rita Adriana; Badiali, Luca; Bondioli, Lucia; Ruozi, Barbara; Vergoni, Anna Valeria; Rivasi, Francesco; Benassi, Rois; Vandelli, Maria Angela; Forni, Flavio. - STAMPA. - 1(2010), pp. 84-84. ((Intervento presentato al convegno Neuroscience 2010 tenutosi a San Diego, CA, US nel 13-17 November 2010.|
|Tipologia||Relazione in Atti di Convegno|
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