title: Influence of chitosan coating on magnetic nanoparticles in endothelial cells and acute tissue biodistribution.
abstract: Chitosan coating on magnetic nanoparticles (MNPs) was studied on biological systems as a first step toward the application in the biomedical field as drug-targeted nanosystems. Composition of MNPs consists of magnetite functionalized with oleic acid and coated with the biopolymer chitosan or glutaraldehyde-cross-linked chitosan. The influence of the biopolymeric coating has been evaluated by in vitro and in vivo assays on the effects of these MNPs on rat aortic endothelial cells (ECs) viability and on the random tissue distribution in mice. Results were correlated with the physicochemical properties of the nanoparticles. Nitric oxide (NO) production by ECs was determined, considering that endothelial NO represents one of the major markers of ECs function. Cell viability was studied by MTT assay. Different doses of the MNPs (1, 10 and 100 μg/mL) were assayed, revealing that MNPs coated with non-cross-linked chitosan for 6 and 24 h did not affect neither NO production nor cell viability. However, a significant decrease in cell viability was observed after 36 h treatment with the highest dose of this nanocarrier. It was also revealed that the presence and dose of glutaraldehyde in the MNPs structureimpact on the cytotoxicity. The study of the acute tissue distribution was performed acutely in mice after 24 h of an intraperitoneal injection of the MNPs and sub acutely, after 28 days of weekly administration. Both formulations greatly avoided the initial clearance by the reticuloendothelial system (RES) in liver. Biological properties found for N1 and N2 in the performed assays reveal that chitosan coating improves biocompatibility of MNPs turning these magnetic nanosystems as promising devices for targeted drug delivery.
authors.affiliation: a INQUISUR, UNS, CONICET, Departamento de Química , Universidad Nacional del Sur , Avda. Alem 1253, B8000CPB, Bahía Blanca , Argentina.
authors.forename: Mariela
authors.initials: M
authors.lastname: Agotegaray
authors.affiliation: b INBIOSUR, UNS, CONICET, DBByF , Universidad Nacional del Sur , San Juan 670, 8000, Bahía Blanca , Argentina.
authors.forename: Adrián
authors.initials: A
authors.lastname: Campelo
authors.affiliation: c CNEA, Centro Atómico Bariloche , Div. Resonancias Magnéticas, CONICET , Avda. Bustillo Km. 9,5, 8400 - San Carlos de Bariloche , Argentina.
authors.forename: Roberto
authors.initials: R
authors.lastname: Zysler
authors.affiliation: b INBIOSUR, UNS, CONICET, DBByF , Universidad Nacional del Sur , San Juan 670, 8000, Bahía Blanca , Argentina.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Gumilar
authors.affiliation: b INBIOSUR, UNS, CONICET, DBByF , Universidad Nacional del Sur , San Juan 670, 8000, Bahía Blanca , Argentina.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bras
authors.affiliation: b INBIOSUR, UNS, CONICET, DBByF , Universidad Nacional del Sur , San Juan 670, 8000, Bahía Blanca , Argentina.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Minetti
authors.affiliation: b INBIOSUR, UNS, CONICET, DBByF , Universidad Nacional del Sur , San Juan 670, 8000, Bahía Blanca , Argentina.
authors.forename: Virginia
authors.initials: V
authors.lastname: Massheimer
authors.affiliation: a INQUISUR, UNS, CONICET, Departamento de Química , Universidad Nacional del Sur , Avda. Alem 1253, B8000CPB, Bahía Blanca , Argentina.
authors.forename: Verónica
authors.initials: V
authors.lastname: Lassalle
mesh_terms: D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005079:Excipients; D005260:Female; D005976:Glutaral / Q000737:chemistry; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D019301:Oleic Acid / Q000737:chemistry; D010316:Particle Size; D017208:Rats, Wistar; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005079:Excipients; D058185:Magnetite Nanoparticles; D019301:Oleic Acid; D009569:Nitric Oxide; D048271:Chitosan; D005976:Glutaral
keywords: Magnetic carriers; biodistribution; chitosan; endothelial cells; nanoparticles