Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility

Jan Zaloga,1 Christina Janko,1 Johannes Nowak,2 Jasmin Matuszak,1 Sabine Knaup,1 Dietmar Eberbeck,3 Rainer Tietze,1 Harald Unterweger,1 Ralf P Friedrich,1 Stephan Duerr,1 Ralph Heimke-Brinck,4 Eva Baum,4 Iwona Cicha,1 Frank Dörje,4 Stefan Odenbach,2 Stefan Lyer,1 Geoffrey Lee,5 Christoph A...

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Autores principales:	Zaloga J, Janko C, Nowak J, Matuszak J, Knaup S, Eberbeck D, Tietze R, Unterweger H, Friedrich RP, Duerr S, Heimke-Brinck R, Baum E, Cicha I, Dörje F, Odenbach S, Lyer S, Lee G, Alexiou C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/93d1d37bec054008bb9a0b63b7dfbf18
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spelling	oai:doaj.org-article:93d1d37bec054008bb9a0b63b7dfbf182021-12-02T04:23:13ZDevelopment of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility1178-2013https://doaj.org/article/93d1d37bec054008bb9a0b63b7dfbf182014-10-01T00:00:00Zhttp://www.dovepress.com/development-of-a-lauric-acidalbumin-hybrid-iron-oxide-nanoparticle-sys-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Jan Zaloga,1 Christina Janko,1 Johannes Nowak,2 Jasmin Matuszak,1 Sabine Knaup,1 Dietmar Eberbeck,3 Rainer Tietze,1 Harald Unterweger,1 Ralf P Friedrich,1 Stephan Duerr,1 Ralph Heimke-Brinck,4 Eva Baum,4 Iwona Cicha,1 Frank Dörje,4 Stefan Odenbach,2 Stefan Lyer,1 Geoffrey Lee,5 Christoph Alexiou1 1Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany; 2Measuring and Automation Technology, Technical University Dresden, Dresden, Germany; 3Physikalisch-Technische-Bundesanstalt, Berlin, Germany; 4Pharmacy Department, University Hospital Erlangen, Erlangen, Germany; 5Division of Pharmaceutics, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany 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. Keywords: iron oxide nanoparticles, drug delivery, protein corona, magnetic drug targeting, colloidal stabilityZaloga JJanko CNowak JMatuszak JKnaup SEberbeck DTietze RUnterweger HFriedrich RPDuerr SHeimke-Brinck RBaum ECicha IDörje FOdenbach SLyer SLee GAlexiou CDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4847-4866 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Zaloga J Janko C Nowak J Matuszak J Knaup S Eberbeck D Tietze R Unterweger H Friedrich RP Duerr S Heimke-Brinck R Baum E Cicha I Dörje F Odenbach S Lyer S Lee G Alexiou C Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility
description	Jan Zaloga,1 Christina Janko,1 Johannes Nowak,2 Jasmin Matuszak,1 Sabine Knaup,1 Dietmar Eberbeck,3 Rainer Tietze,1 Harald Unterweger,1 Ralf P Friedrich,1 Stephan Duerr,1 Ralph Heimke-Brinck,4 Eva Baum,4 Iwona Cicha,1 Frank Dörje,4 Stefan Odenbach,2 Stefan Lyer,1 Geoffrey Lee,5 Christoph Alexiou1 1Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung-Professorship, University Hospital Erlangen, Erlangen, Germany; 2Measuring and Automation Technology, Technical University Dresden, Dresden, Germany; 3Physikalisch-Technische-Bundesanstalt, Berlin, Germany; 4Pharmacy Department, University Hospital Erlangen, Erlangen, Germany; 5Division of Pharmaceutics, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany 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. Keywords: iron oxide nanoparticles, drug delivery, protein corona, magnetic drug targeting, colloidal stability
format	article
author	Zaloga J Janko C Nowak J Matuszak J Knaup S Eberbeck D Tietze R Unterweger H Friedrich RP Duerr S Heimke-Brinck R Baum E Cicha I Dörje F Odenbach S Lyer S Lee G Alexiou C
author_facet	Zaloga J Janko C Nowak J Matuszak J Knaup S Eberbeck D Tietze R Unterweger H Friedrich RP Duerr S Heimke-Brinck R Baum E Cicha I Dörje F Odenbach S Lyer S Lee G Alexiou C
author_sort	Zaloga J
title	Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility
title_short	Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility
title_full	Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility
title_fullStr	Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility
title_full_unstemmed	Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility
title_sort	development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/93d1d37bec054008bb9a0b63b7dfbf18
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Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility

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