title: Development of Blood-Brain Barrier Permeable Nanoparticles as Potential Carriers for Salvianolic Acid B to CNS.
abstract: The blood-brain barrier hinders the passage of systemically delivered therapeutics and the brain extracellular matrix limits the distribution and durability of locally delivered agents. Drug-loaded nanocarriers represent a promising strategy to overcome these barriers and address specific drug delivery challenges due to their small size and versatile design. We synthetized [fluorescent poly(ethyl-cyanoacrylate) nanoparticles coated with Tween 80 by an emulsion polymerization method to target and reach the brain after intravenous and intraperitoneal administration. Nanoparticles were characterized in terms of dimensional analysis, polydispersity and zeta potential (ζ-potential), morphology, encapsulation efficacy, and loading capacity. After intracerebral injection in healthy rats, nanoparticles were distributed within the injected hemisphere and mainly interacted with microglial cells, presumably involved in their clearance by phagocytosis. Furthermore, nanoparticles were able to pass the blood-brain barrier after systemic administration in rats, and the lack of toxicity in C57/B6 mice chronically administered was highlighted. The data obtained helped to clarify the nanoparticles distribution, accumulation, fate, and toxicity into the brain. The selected nanoparticles may represent a biocompatible promising carrier to be further investigated as brain delivery systems. Salvianolic acid B fromSalvia miltiorrhizais a promising molecule in the protection of degeneration in several animal models by various biological mechanisms, but its poor chemical stability and low bioavailability limits its clinical application for central nervous system neuronal injury and degeneration. Nanoparticles were loaded with salvianolic acid B obtaining an encapsulation efficacy and loading capacities of 98.70 % ± 0.45 and 53.3 % ± 0.24, respectively. They were suitable for parental administration because their mean diameter was smaller than 300 nm, with a polydispersity of 0.04 ± 0.03, and aζ-potential of - 8.38 mV ± 3.87. Thein vitrorelease of salvianolic acid B from the nanoparticles was sustained and prolonged during 8 h, suitable for a promising clinical application.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Division of Pharmacology and Toxicology, University of Florence, Florence, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grossi
authors.affiliation: Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Sesto Fiorentino (FI), Florence, Italy.
authors.forename: Clizia
authors.initials: C
authors.lastname: Guccione
authors.affiliation: Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Sesto Fiorentino (FI), Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Isacchi
authors.affiliation: Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Sesto Fiorentino (FI), Florence, Italy.
authors.forename: Maria Camilla
authors.initials: MC
authors.lastname: Bergonzi
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Division of Pharmacology and Toxicology, University of Florence, Florence, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Luccarini
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Division of Pharmacology and Toxicology, University of Florence, Florence, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Casamenti
authors.affiliation: Department of Chemistry, Building of Pharmaceutical Sciences, University of Florence, Sesto Fiorentino (FI), Florence, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bilia
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage*; D001672:Biocompatible Materials; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D003487:Cyanoacrylates; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D027561:Salvia miltiorrhiza / Q000737:chemistry; D053630:Depsides
chemical_list: D001572:Benzofurans; D001672:Biocompatible Materials; D003487:Cyanoacrylates; D004337:Drug Carriers; C558475:poly(ethylcyanoacrylate); C076944:salvianolic acid B; D053630:Depsides