Non-invasive strategies for treatment of Central Nervous System (CNS) diseases based on colloidal carriers represent a huge potential to efficiently transport drug across the BBB, since nanocarriers can protect drugs (or gene material) and deliver them to target specific populations of brain cells. The efficacy of the nanotechnological approach for brain targeting has been proved by several papers and widely reviewed. Literature contributions mainly deal with several kind of nanometric carriers such as polymeric nanoparticles (NPs), liposomes, solid-lipid NPs, micelles, nanogels and dendrimers. However, these nanocarriers, target and reach the brain poorly, if not engineered in their surface to take advantage of BBB transport mechanisms. Recent studies demonstrated the efficacy of the medicinal chemistry approach, based on the modification of the physico-chemical properties of drugs and the biological approach, based on the conjugation of molecules with antibodies or ligands targeting the BBB. In this contest, polymeric nanoparticles (NPs) and liposomes (LPs) were formulated and specifically engineered to cross the BBB and arrive to CNS and proposed to encapsulate an deliver cholesterol an BDNF to the CNS. Our attention point on the use of polymeric nanoparticles engineered on surface by a selective ligand able to promote the NPs crossing of BBB. In fact, preliminary studies demonstrated the ability of new targeted polymeric poly-lactide-co-glycolide (PLGA) NPs modified with a short peptide (H2N-Gly-L-Phe-D-Thr-Gly-L-Phe-L-Leu-L-Ser(O-β-D-Glucose)-CONH2 (g7-NPs) to create BBB interaction and trigger an efficacious BBB crossing delivering of active. In particular, several in vivo biodistribution studies and pharmacological proof-of-evidence of brain delivery of model drugs (not able by themselves to reach the brain, as Rhodamine-123 and Loperamide) demonstrated the ability of g7-NPs to create BBB interaction and trigger an efficacious BBB crossing. A total biodistibution of g7-NPs, obtained after i.v. administration in rats, evidenced a strong and significant localization of the g7-NPs into CNS in a quantity about two orders of magnitude greater (10-15%) than that found with the other known NP drug carriers. More recently, the g7-NP BBB crossing mechanism was investigated, pointing out an interaction between g7-NPs and BBB and endocytosis/macropinocytosis pathways for BBB crossing. Same results were pointed out also in vitro on neurons/glia cell coltures, evidencing the endocytotic pathways as g7-NPs cell entrance as well as the assessing of the safety of g7-NPs not creating any damage to cells even at high doses.

Nanomedicine in Neuroscience: The potential of targeted nanoparticles in neurodegenerative disorders / Tosi, Giovanni; Ruozi, Barbara; Vilella, Antonietta; Belletti, Daniela; Veratti, Patrizia; Baraldi, Elisa; Zoli, Michele; M., Schmeisser; A., Grabrucker; H. S., Sharma; A., Sharma; Forni, Flavio; Vandelli, Maria Angela. - STAMPA. - (2012), pp. 520.04-520.04. (Intervento presentato al convegno SfN 2012 tenutosi a New Orleans nel 13-18 October 2012).

Nanomedicine in Neuroscience: The potential of targeted nanoparticles in neurodegenerative disorders

TOSI, Giovanni;RUOZI, Barbara;VILELLA, ANTONIETTA;BELLETTI, Daniela;VERATTI, PATRIZIA;BARALDI, ELISA;ZOLI, Michele;FORNI, Flavio;VANDELLI, Maria Angela
2012

Abstract

Non-invasive strategies for treatment of Central Nervous System (CNS) diseases based on colloidal carriers represent a huge potential to efficiently transport drug across the BBB, since nanocarriers can protect drugs (or gene material) and deliver them to target specific populations of brain cells. The efficacy of the nanotechnological approach for brain targeting has been proved by several papers and widely reviewed. Literature contributions mainly deal with several kind of nanometric carriers such as polymeric nanoparticles (NPs), liposomes, solid-lipid NPs, micelles, nanogels and dendrimers. However, these nanocarriers, target and reach the brain poorly, if not engineered in their surface to take advantage of BBB transport mechanisms. Recent studies demonstrated the efficacy of the medicinal chemistry approach, based on the modification of the physico-chemical properties of drugs and the biological approach, based on the conjugation of molecules with antibodies or ligands targeting the BBB. In this contest, polymeric nanoparticles (NPs) and liposomes (LPs) were formulated and specifically engineered to cross the BBB and arrive to CNS and proposed to encapsulate an deliver cholesterol an BDNF to the CNS. Our attention point on the use of polymeric nanoparticles engineered on surface by a selective ligand able to promote the NPs crossing of BBB. In fact, preliminary studies demonstrated the ability of new targeted polymeric poly-lactide-co-glycolide (PLGA) NPs modified with a short peptide (H2N-Gly-L-Phe-D-Thr-Gly-L-Phe-L-Leu-L-Ser(O-β-D-Glucose)-CONH2 (g7-NPs) to create BBB interaction and trigger an efficacious BBB crossing delivering of active. In particular, several in vivo biodistribution studies and pharmacological proof-of-evidence of brain delivery of model drugs (not able by themselves to reach the brain, as Rhodamine-123 and Loperamide) demonstrated the ability of g7-NPs to create BBB interaction and trigger an efficacious BBB crossing. A total biodistibution of g7-NPs, obtained after i.v. administration in rats, evidenced a strong and significant localization of the g7-NPs into CNS in a quantity about two orders of magnitude greater (10-15%) than that found with the other known NP drug carriers. More recently, the g7-NP BBB crossing mechanism was investigated, pointing out an interaction between g7-NPs and BBB and endocytosis/macropinocytosis pathways for BBB crossing. Same results were pointed out also in vitro on neurons/glia cell coltures, evidencing the endocytotic pathways as g7-NPs cell entrance as well as the assessing of the safety of g7-NPs not creating any damage to cells even at high doses.
2012
SfN 2012
New Orleans
13-18 October 2012
520.04
520.04
Tosi, Giovanni; Ruozi, Barbara; Vilella, Antonietta; Belletti, Daniela; Veratti, Patrizia; Baraldi, Elisa; Zoli, Michele; M., Schmeisser; A., Grabruck...espandi
Nanomedicine in Neuroscience: The potential of targeted nanoparticles in neurodegenerative disorders / Tosi, Giovanni; Ruozi, Barbara; Vilella, Antonietta; Belletti, Daniela; Veratti, Patrizia; Baraldi, Elisa; Zoli, Michele; M., Schmeisser; A., Grabrucker; H. S., Sharma; A., Sharma; Forni, Flavio; Vandelli, Maria Angela. - STAMPA. - (2012), pp. 520.04-520.04. (Intervento presentato al convegno SfN 2012 tenutosi a New Orleans nel 13-18 October 2012).
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