title: Exploiting Bacterial Pathways for BBB Crossing with PLGA Nanoparticles Modified with a Mutated Form of Diphtheria Toxin (CRM197): In Vivo Experiments.
abstract: Drugs can be targeted to the brain using polymeric nanoparticles (NPs) engineered on their surface with ligands able to allow crossing of the blood-brain barrier (BBB). This article aims to investigate the BBB crossing efficiency of polymeric poly lactide-co-glycolide (PLGA) NPs modified with a mutated form of diphtheria toxin (CRM197) in comparison with the results previously obtained using PLGA NPs modified with a glycopeptide (g7-NPs). Different kinds of NPs, covalently coupled PLGA with different fluorescent probes (DY405, rhodamine-B base and DY675) and different ligands (g7 and CRM197) were tested in vivo to assess their behavior and trafficking. The results highlighted the possibility to distinguish the different kinds of simultaneously administered NPs and to emphasize that CRM-197 modified NPs and g7-NPs can cross the BBB at a similar extent. The analysis of BBB crossing and of the neuronal tropism of CRM197 modified NPs, along with their BBB crossing pathways were also developed. In vivo pharmacological studies performed on CRM197 engineered NPs, loaded with loperamide, underlined their ability as drug carriers to the CNS.
authors: Nanomedicine Group, Te.Far.T.I. center, Department of Life Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.|NEST, Istituto Nanoscienze-CNR , Piazza San Silvestro 12, 56127 Pisa, Italy.
authors: G
authors: G
authors: Tosi
authors: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.
authors: A
authors: A
authors: Vilella
authors: Nanomedicine Group, Te.Far.T.I. center, Department of Life Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.
authors: P
authors: P
authors: Veratti
authors: Nanomedicine Group, Te.Far.T.I. center, Department of Life Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.
authors: D
authors: D
authors: Belletti
authors: Nanomedicine Group, Te.Far.T.I. center, Department of Life Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.|NEST, Istituto Nanoscienze-CNR , Piazza San Silvestro 12, 56127 Pisa, Italy.
authors: F
authors: F
authors: Pederzoli
authors: Nanomedicine Group, Te.Far.T.I. center, Department of Life Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.
authors: B
authors: B
authors: Ruozi
authors: Nanomedicine Group, Te.Far.T.I. center, Department of Life Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.
authors: M A
authors: MA
authors: Vandelli
authors: Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.
authors: M
authors: M
authors: Zoli
authors: Nanomedicine Group, Te.Far.T.I. center, Department of Life Sciences, University of Modena and Reggio Emilia , 41124 Modena, Italy.
authors: F
authors: F
authors: Forni
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000382:microbiology; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D008139:Loperamide / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000378:metabolism / Q000627:therapeutic use*; D059225:Nociception / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D004167:Diphtheria Toxin; C028581:CRM197 (non-toxic variant of diphtheria toxin); D008139:Loperamide
keywords: CRM197; brain; drug delivery; nanomedicine; vivo