title: Chitosan coating of copper nanoparticles reduces in vitro toxicity and increases inflammation in the lung.
abstract: Despite their potential for a variety of applications, copper nanoparticles induce very strong inflammatory responses and cellular toxicity following aerosolized delivery. Coating metallic nanoparticles with polysaccharides, such as biocompatible and antimicrobial chitosan, has the potential to reduce this toxicity. In this study, copper nanoparticles were coated with chitosan using a newly developed and facile method. The presence of coating was confirmed using x-ray photoelectron spectroscopy, rhodamine tagging of chitosan followed by confocal fluorescence imaging of coated particles and observed increases in particle size and zeta potential. Further physical and chemical characteristics were evaluated using dissolution and x-ray diffraction studies. The chitosan coating was shown to significantly reduce the toxicity of copper nanoparticles after 24 and 52 h and the generation of reactive oxygen species as assayed by DHE oxidation after 24 h in vitro. Conversely, inflammatory response, measured using the number of white blood cells, total protein, and cytokines/chemokines in the bronchoalveolar fluid of mice exposed to chitosan coated versus uncoated copper nanoparticles, was shown to increase, as was the concentration of copper ions. These results suggest that coating metal nanoparticles with mucoadhesive polysaccharides (e.g. chitosan) could increase their potential for use in controlled release of copper ions to cells, but will result in a higher inflammatory response if administered via the lung.
authors.affiliation: Department of Chemical and Biochemical Engineering, College of Engineering, University of Iowa, Iowa City, IA 52242, USA. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Kristan L S
authors.initials: KL
authors.lastname: Worthington
authors.forename: Andrea
authors.initials: A
authors.lastname: Adamcakova-Dodd
authors.forename: Amaraporn
authors.initials: A
authors.lastname: Wongrakpanich
authors.forename: Imali A
authors.initials: IA
authors.lastname: Mudunkotuwa
authors.forename: Kranti A
authors.initials: KA
authors.lastname: Mapuskar
authors.forename: Vijaya B
authors.initials: VB
authors.lastname: Joshi
authors.forename: C
authors.initials: C
authors.lastname: Allan Guymon
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Spitz
authors.forename: Vicki H
authors.initials: VH
authors.lastname: Grassian
authors.forename: Peter S
authors.initials: PS
authors.lastname: Thorne
authors.forename: Aliasger K
authors.initials: AK
authors.lastname: Salem
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D048271:Chitosan / Q000008:administration & dosage / Q000494:pharmacology*; D003300:Copper / Q000008:administration & dosage / Q000633:toxicity*; D016207:Cytokines; D006801:Humans; D008168:Lung / Q000737:chemistry; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced*
chemical_list: D016207:Cytokines; D003300:Copper; D048271:Chitosan