title: Novel magnetic iron oxide nanoparticles coated with poly(ethylene imine)-g-poly(ethylene glycol) for potential biomedical application: synthesis, stability, cytotoxicity and MR imaging.
abstract: Magnetic iron oxide nanoparticles have found application as contrast agents for magnetic resonance imaging (MRI) and as switchable drug delivery vehicles. Their stabilization as colloidal carriers remains a challenge. The potential of poly(ethylene imine)-g-poly(ethylene glycol) (PEGPEI) as stabilizer for iron oxide (γ-Fe₂O₃) nanoparticles was studied in comparison to branched poly(ethylene imine) (PEI). Carrier systems consisting of γ-Fe₂O₃-PEI and γ-Fe₂O₃-PEGPEI were prepared and characterized regarding their physicochemical properties including magnetic resonance relaxometry. Colloidal stability of the formulations was tested in several media and cytotoxic effects in adenocarcinomic epithelial cells were investigated. Synthesized γ-Fe₂O₃ cores showed superparamagnetism and high degree of crystallinity. Diameters of polymer-coated nanoparticles γ-Fe₂O₃-PEI and γ-Fe₂O₃-PEGPEI were found to be 38.7 ± 1.0 nm and 40.4 ± 1.6 nm, respectively. No aggregation tendency was observable for γ-Fe₂O₃-PEGPEI over 12 h even in high ionic strength media. Furthermore, IC₅₀ values were significantly increased by more than 10-fold when compared to γ-Fe₂O₃-PEI. Formulations exhibited r₂ relaxivities of high numerical value, namely around 160 mM⁻¹ s⁻¹. In summary, novel carrier systems composed of γ-Fe₂O₃-PEGPEI meet key quality requirements rendering them promising for biomedical applications, e.g. as MRI contrast agents.
authors.affiliation: Department of Pharmaceutics and Biopharmacy, Philipps-Universität Marburg, Ketzerbach 63, 35037 Marburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schweiger
authors.forename: Clemens
authors.initials: C
authors.lastname: Pietzonka
authors.forename: Johannes
authors.initials: J
authors.lastname: Heverhagen
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D020811:Biomedical Technology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002627:Chemistry, Physical; D003102:Colloids; D003287:Contrast Media / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D005290:Ferric Compounds / Q000737:chemistry*; D006801:Humans; D057446:Hydrodynamics; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
chemical_list: D003102:Colloids; D003287:Contrast Media; D004337:Drug Carriers; D005290:Ferric Compounds; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); C000499:ferric oxide; D011092:Polyethylene Glycols; D011094:Polyethyleneimine