title: Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility.
abstract: The promising potential of superparamagnetic iron oxide nanoparticles (SPIONs) in various nanomedical applications has been frequently reported. However, although many different synthesis methods, coatings, and functionalization techniques have been described, not many core-shell SPION drug delivery systems are available for clinicians at the moment. Here, bovine serum albumin was adsorbed onto lauric acid-stabilized SPIONs. The agglomeration behavior, zeta potential, and their dependence on the synthesis conditions were characterized with dynamic light scattering. The existence and composition of the core-shell-matrix structure was investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta potential measurements. We showed that the iron oxide cores form agglomerates in the range of 80 nm. Moreover, despite their remarkably low tendency to aggregate even in a complex media like whole blood, the SPIONs still maintained their magnetic properties and were well attractable with a magnet. The magnetic properties were quantified by vibrating sample magnetometry and a superconducting quantum interference device. Using flow cytometry, we further investigated the effects of the different types of nanoparticle coating on morphology, viability, and DNA integrity of Jurkat cells. We showed that by addition of bovine serum albumin, the toxicity of nanoparticles is greatly reduced. We also investigated the effect of the particles on the growth of primary human endothelial cells to further demonstrate the biocompatibility of the particles. As proof of principle, we showed that the hybrid-coated particles are able to carry payloads of up to 800 μg/mL of the cytostatic drug mitoxantrone while still staying colloidally stable. The drug-loaded system exhibited excellent therapeutic potential in vitro, exceeding that of free mitoxantrone. In conclusion, we have synthesized a biocompatible ferrofluid that shows great potential for clinical application. The synthesis is straightforward and reproducible and thus easily translatable into a good manufacturing practice environment.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Zaloga
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Janko
authors.affiliation: Measuring and Automation Technology, Technical University Dresden, Dresden, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Nowak
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Matuszak
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Knaup
authors.affiliation: Physikalisch-Technische-Bundesanstalt, Berlin, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Eberbeck
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Tietze
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Unterweger
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Friedrich
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Duerr
authors.affiliation: Pharmacy Department, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Heimke-Brinck
authors.affiliation: Pharmacy Department, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Baum
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Iwona
authors.initials: I
authors.lastname: Cicha
authors.affiliation: Pharmacy Department, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Dörje
authors.affiliation: Measuring and Automation Technology, Technical University Dresden, Dresden, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Odenbach
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lyer
authors.affiliation: Division of Pharmaceutics, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Alexiou
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003102:Colloids / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D004492:Edetic Acid; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019169:Jurkat Cells; D007850:Lauric Acids / Q000737:chemistry*; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D008942:Mitoxantrone / Q000737:chemistry / Q000493:pharmacokinetics; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D001672:Biocompatible Materials; D003102:Colloids; D007850:Lauric Acids; D058185:Magnetite Nanoparticles; C030358:lauric acid; D012710:Serum Albumin, Bovine; D004492:Edetic Acid; D008942:Mitoxantrone
keywords: colloidal stability; drug delivery; iron oxide nanoparticles; magnetic drug targeting; protein corona