title: Local Effects on Airway Inflammation and Systemic Uptake of 5 nm PEGylated and Citrated Gold Nanoparticles in Asthmatic Mice.
abstract: Nanotechnology is showing promise in many medical applications such as drug delivery and hyperthermia. Nanoparticles administered to the respiratory tract cause local reactions and cross the blood-air barrier, thereby providing a means for easy systemic administration but also a potential source of toxicity. Little is known about how these effects are influenced by preexisting airway diseases such as asthma. Here, BALB/c mice are treated according to the ovalbumin (OVA) asthma protocol to promote allergic airway inflammation. Dispersions of polyethylene-glycol-coated (PEGylated) and citrate/tannic-acid-coated (citrated) 5 nm gold nanoparticles are applied intranasally to asthma and control groups, and (i) airway resistance and (ii) local tissue effects are measured as primary endpoints. Further, nanoparticle uptake into extrapulmonary organs is quantified by inductively coupled plasma mass spectrometry. The asthmatic precondition increases nanoparticle uptake. Moreover, systemic uptake is higher for PEGylated gold nanoparticles compared to citrated nanoparticles. Nanoparticles inhibit both inflammatory infiltrates and airway hyperreactivity, especially citrated gold nanoparticles. Although the antiinflammatory effects of gold nanoparticles might be of therapeutic benefit, systemic uptake and consequent adverse effects must be considered when designing and testing nanoparticle-based asthma therapies.
authors.affiliation: Department of Experimental Pneumology and Allergology, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Omlor
authors.affiliation: Department of Experimental Pneumology and Allergology, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Duc D
authors.initials: DD
authors.lastname: Le
authors.affiliation: Department of Experimental Pneumology and Allergology, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Schlicker
authors.affiliation: Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hannig
authors.affiliation: Department of Experimental Pneumology and Allergology, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Raphael
authors.initials: R
authors.lastname: Ewen
authors.affiliation: Department of Experimental Pneumology and Allergology, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heck
authors.affiliation: Department of Internal Medicine V, Pneumology, Allergology and Respiratory Critical Care Medicine, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herr
authors.affiliation: INM-Leibniz Institute for New Materials, Campus D2 2, D-66123, Saarbrücken, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Kraegeloh
authors.affiliation: Institute of Inorganic Solid State Chemistry, Saarland University, Campus Dudweiler, Am Markt Zeile 3-5, D-66125, Saarbrücken, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Hein
authors.affiliation: Institute of Inorganic Solid State Chemistry, Saarland University, Campus Dudweiler, Am Markt Zeile 3-5, D-66125, Saarbrücken, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kautenburger
authors.affiliation: Institute of Inorganic Solid State Chemistry, Saarland University, Campus Dudweiler, Am Markt Zeile 3-5, D-66125, Saarbrücken, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Kickelbick
authors.affiliation: Department of Internal Medicine V, Pneumology, Allergology and Respiratory Critical Care Medicine, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, 303 Kapoor Hall, SUNY Buffalo, NY, 14214, USA.
authors.forename: Juliane
authors.initials: J
authors.lastname: Nguyen
authors.affiliation: Department of Experimental Pneumology and Allergology, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.|Department of Internal Medicine V, Pneumology, Allergology and Respiratory Critical Care Medicine, Saarland University Faculty of Medicine, Kirrberger Str. 100, D-66421, Homburg/Saar, Germany.
authors.forename: Q Thai
authors.initials: QT
authors.lastname: Dinh
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D006046:Gold / Q000737:chemistry*; D013058:Mass Spectrometry; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D036103:Nanotechnology / Q000379:methods*; D010047:Ovalbumin / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D011092:Polyethylene Glycols; D006046:Gold; D010047:Ovalbumin
keywords: ICP-MS; PEG-coating; allergic airway inflammation; antiinflammatory effect; gold nanoparticles